Method for modifying the refractive index of an optical material and resulting optical vision component

ABSTRACT

A method for modifying the refractive index of an optical polymeric material. The method comprises continuously irradiating predetermined regions of an optical, polymeric material with femtosecond laser pulses to form a gradient index refractive structure within the material. The optical polymeric material can include a photosensitizer to increase the photoefficiency of the two-photo process resulting in the formation of the observed refractive structures. An optical device includes an optical, polymeric lens material having an anterior surface and posterior surface and an optical axis intersecting the surfaces and at least one laser-modified, GRIN layer disposed between the anterior surface and the posterior surface and arranged along a first axis 45° to 90° to the optical axis. The at least one laser-modified GRIN layer comprises a plurality of adjacent refractive segments characterized by a variation in index of refraction across at least one of at least a portion of the adjacent segments and along each segment.

CROSS REFERENCE

This application is a continuation of pending application Ser. No.14/849,058 filed on Sep. 9, 2015, now U.S. Pat. No. 9,939,558, which isa divisional of application Ser. No. 13/238,143 filed on Sep. 21, 2011,now U.S. Pat. No. 9,144,491, which further claims the benefit under 35USC 119(e) of Provisional Patent Application No. 61/492,586 filed Jun.2, 2011, the disclosures of which are hereby incorporated by referenceherein in their entireties.

CREATE Act Statement: The claimed invention was made by, on behalf of,or in connection with one or more of the following parties to a jointuniversity-corporation research agreement: The University of Rochester,and Bausch & Lomb, Inc. The agreement was in effect on and before thedate the claimed invention was made, and the claimed invention was madeas a result of activities undertaken within the scope of the agreement.

FIELD OF THE INVENTION

Embodiments of the invention are directed to a method for using a laserto modify the refractive properties of optical components or devicessuch as, but not limited to, intraocular lenses (IOLs), contact lenses,corneal inlays, and other such optical components or devices thatinclude hydrogel or hydrophobic acrylate materials, the resultingoptical components or devices, and other applications.

DESCRIPTION OF RELATED ART

In general, there are two types of intraocular lenses, referred to aspseudo-phakic IOLs and phakic IOLs. The former type replaces the eye'snatural, crystalline lens, usually to replace a cataractous lens thathas been removed. The latter type is used to supplement an existing lensand functions as a permanent corrective lens, which is implanted in theanterior or posterior chamber to correct refractive errors of the eye.The power of the lens (i.e., point focus on the retina from lightoriginating at infinity) to be implanted is determined based onpre-operative measurements of ocular length and corneal curvature ofeach patient. The pre-operative measurements are conducted with the hopethat the patient will need little, if any, vision correction followingthe surgery. Unfortunately, due to errors in measurement, variable lenspositioning, or wound healing, most patients undergoing surgery will notenjoy optimal vision without some form of vision correction followingthe surgery. Since the power of a typical (non-accommodating) IOL isfixed and cannot be adjusted post-implantation (in-situ), most patientsmust use corrective lenses such as eye glasses or contact lensesfollowing cataract surgery to optimize their vision.

One potential alternative to post-operative, corrective lenses is alight-adjustable intraocular lens whose refractive properties can bemodified following insertion of the lens into a human eye. Such a lensis reported in U.S. Pat. No. 6,450,642, hereafter referred to as theCalhoun Patent. The light-adjustable lens is said to comprise (i) afirst polymer matrix and (ii) a refraction modulating composition (RMC)that is capable of stimulus-induced polymerization. As stated, when aportion of the described lens is exposed to light of sufficientintensity, the RMC forms a second polymer matrix. The process is said toresult in a light adjusted, power-modified lens.

As described in the Calhoun Patent, the first polymer matrix and the RMCare selected such that the components that comprise the RMC are capableof diffusion within the first polymer matrix. Put another way, a loosefirst polymer matrix will tend to be paired with larger RMC componentsand a tight first polymer matrix will tend to be paired with smaller RMCcomponents. Upon exposure to an appropriate energy source (e.g., heat orlight), the RMC typically forms a second polymer matrix in the exposedregion of the optical element. After exposure, the RMC in the unexposedregion will migrate into the exposed region over time. The amount of RMCmigration into the exposed region is said to be time dependent andcontrollable. If enough time is permitted, the RMC components willre-equilibrate and redistribute throughout the lens material (i.e., thefirst polymer matrix, including the exposed region). When the region isre-exposed to the energy source, the RMC that has since migrated intothe region polymerizes to further increase the formation of the secondpolymer matrix. This process (exposure followed by an appropriate timeinterval to allow for diffusion) may be repeated until the exposedregion of the optical element has reached the desired property (e.g.,power, refractive index, or shape). The entire optical element is thenexposed to an energy source to “lock-in” the desired lens property bypolymerizing the remaining RMC in the lens material. Overall, the powerof the lens is changed by a shape change caused by the migration of theRMC and subsequent polymerization(s).

U.S. Pat. No. 7,105,110 describes a method and instrument to irradiate alight adjustable lens as described in the Calhoun Patent with anappropriate amount of radiation in an appropriate pattern. The method issaid to include aligning a source of the modifying radiation so as toimpinge the radiation onto the lens in a pattern, and controlling thequantity of the impinging radiation. The quantity of the impingingradiation is controlled by controlling the intensity and duration of theirradiation.

Applicants have previously described methods for modifying therefractive index of optical polymeric materials using very short pulsesfrom a visible or near-IR laser having a pulse energy from 0.5 nJ to1000 nJ. See, U.S. Publication No. 2008/0001320. The intensity of lightis sufficient to change the refractive index of the material within thefocal volume, whereas portions just outside the focal volume areminimally affected by the laser light. Irradiation within the focalvolume results in refractive optical structures characterized by apositive change in refractive index of 0.005 or more relative to theindex of refraction of the bulk (non-irradiated) polymeric material.Under certain irradiation conditions and in certain optical materials, achange in refractive index of 0.06 was measured. The irradiated regionsof the optical material can take the form of two- or three-dimensional,area or volume filled refractive structures. The refractive structuresare formed by scanning the laser over a select region of the polymericmaterial resulting in refractive optical structures that can providespherical, aspherical, toroidal, or cylindrical correction to a lens. Infact, any optical structure can be formed to yield positive or negativepower corrections to the lens. Moreover, the optical structures can bestacked vertically or written in separate planes in the polymericmaterial to act as a single lens element. In U.S. Pat. No. 7,789,910Applicants describe using Raman spectroscopy as an investigativeapproach to determine what, if any, structural, chemical or molecularchange is occurring within the focal volume of the optical polymericmaterials that might explain the observed change in the index ofrefraction.

In U.S. Publication No. 2009/0287306, Applicants describe a similarprocess to provide dioptic power changes in optical polymeric materialsthat contain a photosensitizer. The photosensitizer is present in thepolymeric material to enhance the photoefficiency of the two-photonprocess used to form the refractive structures. In some instances, therate at which the laser light is scanned across the polymeric materialcan be increased 100-fold with the inclusion of a photosensitizer andstill provide a similar change in the refractive index of the material.

U.S. Publication No. 2009/0157178 is said to describe a polymericintraocular lens material that can provide a photoinduced, chemicalchange in the material resulting in a change in focal length (power) orthe aspheric character of the lens by modifying the index of refractionof the material with laser light. The photoinduced chemistry in thematerial is said to occur by exposure of the material to laser lightover a broad spectral range of 200 nm to 1500 nm. In the case of UVlight from 200 nm to 400 nm the photoinduced chemistry is said to be asingle-photon process, whereas a two-photon process is envisioned withlight from 400 to 1500 nm. Only photoinduced chemistry using a laserpulse of 313 nm and a total irradiation dose ranging from 0.05 J/cm² to2 J/cm² is described, which is not surprising to Applicants. Early on,Applicants had investigated a similar bond-breaking/bond formationapproach in the hopes of inducing optical changes in polymericmaterials. Applicants learned that light in the UV was necessary, and aphoto-efficient, two-photon process remained elusive for inducing suchchemical or structural changes as well observed changes in the index ofrefraction of the material.

U.S. Publication No. 2010/0228345 is said to describe a lens such as anintraocular lens in which the refractive index within the laser focus(loci) are modified to a depth of 5 μm to 50 μm. The method is said toprovide dioptic power changes to the lens by a change in refractiveindex (Δn) of the lens material at different locus positions, e.g.,between a lowest value of Δn=0.001 to a highest value of Δn=0.01,exploiting a modulo 2n phase wrapping technique. The describedirradiation method uses bursts of femtosecond (fs) laser pulses tochange the refractive index of the irradiated material through amultiphoton absorption mechanism. However, to achieve the desireddioptic changes the resulting modified index optical layers in thematerial must be at least 50 microns (μm) thick.

There is an ongoing need for new and improved techniques and materials,and vision components resulting therefrom, for improving human vision.Such components may include IOLs for use following cataract surgery, ormay be in the form of corneal inlays or other implantable visioncorrection devices. There are also advantages and benefits that wouldresult from such techniques and components allowing in-situ modificationof refractive properties (e.g., refractive index, dioptric power).

SUMMARY

An embodiment of the invention is directed to a method for providingchanges in refractive power of an optical device. The method includes astep of providing an optical device with an optical, polymeric lensmaterial having an anterior surface and posterior surface and an opticalaxis intersecting the surfaces. The method also includes the step offorming at least one laser-modified, gradient index (GRIN) layerdisposed between the anterior surface and the posterior surface withlight pulses from a visible or near-IR laser and scanning the pulsesalong regions of the optical, polymeric material. The at least onelaser-modified GRIN layer comprises a plurality of adjacent refractivesegments, and is further characterized by a variation in index ofrefraction of at least one of: (i) a portion of the adjacent refractivesegments transverse to the direction scanned; and (ii) a portion ofrefractive segments along the direction scanned. In various non-limitingaspects:

-   -   the at least one laser-modified, GRIN layer is arranged along a        first axis and is tilted from between about 45° to 135° to the        optical axis;    -   the polymeric lens material includes a photosensitizer;    -   the photosensitizer includes at least one two-photon absorption        chromophore having a two-photon cross-section of at least 10 GM        between 750 nm and 1100 nm;    -   the photosensitizer is part of a polymerizable monomer or is        physically dispersed within the optical polymer;    -   forming the at least one laser-modified, gradient index GRIN        layer includes irradiating select regions of the optical,        polymeric lens material with a continuous stream of laser pulses        having a pulse energy from 0.01 nJ to 20 nJ;    -   focusing a plurality of very short laser pulses having a defined        focal volume, with a spectral wavelength of between about 650        nanometers (nm) to about 950 nm, into the material. The laser        pulses have a repetition rate from 10 MHz to 300 MHz, a pulse        duration of 10 fs to 500 fs, an average power from 20 mW to 260        mW, and a pulse energy from 0.01 nJ to 20 nJ;    -   the optical device is an intraocular lens whose refractive        properties are modified prior to the surgical insertion of the        lens in a human eye. In this aspect, the irradiation process may        be performed in a manufacturing environment. The refractive        properties may be designed to enhance the depth of field of the        lens or create select regions of variable power to custom fit        the lens to the vision correction needs of a patient.        Alternatively, the refractive properties may be designed to        create a multifocal lens;    -   the optical device is an intraocular lens, or corneal inlay, and        the forming of the at least one laser-modified GRIN layer is        performed following the surgical placement of the optical device        in an eye of a patient, by e.g., an ophthalmic practitioner;    -   the plurality of adjacent refractive segments of the GRIN layer        has an independent line width of one to five μm and the        intersegment spacing of two adjacent refractive segments is less        than an average linewidth of the two adjacent segments;    -   the plurality of adjacent refractive segments are line segments;    -   the plurality of adjacent reftactive segments are concentric        segments outwardly projected from a central point along a first        axis;    -   the plurality of adjacent refractive segments are arcuate or        curved segments;    -   the plurality of segments of the GRIN layer are characterized by        a constant positive change in the index of refraction of at        least one of: —(i) a portion of refractive segments in the        direction scanned; and (ii) along a portion of an axis that is        transverse to the refractive segments, in relation to the index        of refraction of the lens material;    -   the plurality of segments of the GRIN layer are characterized by        a constant rate of increasing or decreasing positive change in        the index of refraction of at least one of: (i) a portion of        refractive segments in the direction scanned; and (ii) along a        portion of an axis that is transverse to the refractive        segments, in relation to the index of refraction of the lens        material;    -   the at least one laser-modified, GRIN layer has a quadratic        profile;    -   the at least one laser-modified, GRIN layer exhibits little or        no scattering loss, i.e., the formed GRIN layer is not clearly        visible under appropriate magnification without phase-contrast        enhancement such that the GRIN layer is virtually transparent to        the human eye without some form of image enhancement;    -   forming the at least one laser-modified, GRIN layer includes        forming from two to ten laser-modified, GRIN layers;    -   forming the at least one laser-modified, GRIN layer includes        forming from two to ten laser-modified, GRIN layers arranged        either above or below the at least one laser-modified, GRIN        layer along a second axis substantially perpendicular to the        first axis;    -   the GRIN layer has an independent thickness of from 2 μm to 10        μm, and the GRIN layers exhibit little or no scattering loss;    -   the two to ten GRIN layers have an interlayer spacing of        non-modified polymeric lens material having a thickness of from        5 μm to 10 μm.

An embodiment of the invention is directed to an optical device having agradient index structure. The device includes an optical, polymeric lensmaterial having an anterior surface and posterior surface and an opticalaxis intersecting the surfaces. The device also includes at least onelaser-modified, GRIN layer disposed between the anterior surface and theposterior surface and arranged along a first axis arranged 45° to 135°to the optical axis. The at least one laser-modified GRIN layercomprises a plurality of adjacent refractive segments, and ischaracterized by a variation in index of refraction of at least one of:(i) a transverse cross section of the adjacent refractive segments; and(ii) a lateral cross section of refractive segments. In variousnon-limiting aspects:

-   -   the plurality of adjacent refractive segments are line segments;    -   the plurality of adjacent refractive segments are selected from        the group consisting of concentric and arcuate or curved        segments;    -   the polymeric lens material includes a photosensitizer;    -   the photosensitizer includes a chromophore with a two-photon,        absorption cross section of at least 10 GM between 750 nm and        1100 nm;    -   the plurality of adjacent refractive segments of the GRIN layer        have an independent line width of one to five μm and an        intersegment spacing of two adjacent segments is less than an        average line width of the two adjacent segments;    -   the plurality of refractive segments of the GRIN layer are        characterized by a constant positive change in the index of        refraction along at least one of the first axis and a transverse        second axis, the change in the index of refraction in relation        to non-modified polymeric lens material;    -   the plurality of refractive segments of the GRIN layer are        characterized by a constant or variable rate of increasing or        decreasing positive change in the index of refraction along at        least one of the first axis and a transverse second axis, the        change in the refractive index in relation to non-modified        polymeric lens material;    -   the polymeric lens material is a hydrogel;    -   the device is an intraocular lens or a corneal inlay.

These and other features, attributes, and characteristics of theembodied invention will now be described in detail with reference to theappended drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodied invention will be better understood from the followingdescription and in consideration with the accompanying figures. It is tobe expressly understood, however, that each of the figures are providedto merely illustrate and describe the embodiments of the invention andare not intended to further limit the claimed embodiments of theinvention.

FIG. 1A is a microscope photograph of a line grating written in anoptical, polymeric material produced by laser irradiation;

FIG. 1B is a schematic representation of the microscope photograph ofFIG. 1A;

FIG. 2A is a microscope photograph of a line grating written above andorthogonal to another line grating in an optical, polymeric materialproduced by laser irradiation;

FIG. 2B is a schematic representation of the microscope photograph ofFIG. 2B;

FIG. 3A is a microscope photograph of an array of cylinders etched in anoptical, polymeric material produced by laser irradiation;

FIG. 3B is a schematic representation of the microscope photograph ofFIG. 3A;

FIG. 4A is a microscope photograph of one array of cylinders (20×20)etched above and slightly offset to another array of cylinders (20×20)in an optical, polymeric material produced by laser irradiation;

FIG. 4B is a schematic representation of the microscope photograph ofFIG. 4A;

FIG. 5 is a schematic representation of a three-dimensional structure inan optical, polymeric material that can be produced by laserirradiation;

FIG. 6 is a schematic representation of creating a convex, plano orconcave structure in an optical, polymeric material to yield a positiveor negative correction;

FIG. 7 is a schematic representation of the laser and optical systemused to write the structures shown in FIGS. 1 to 4, 9, 10 and 12;

FIG. 8A is a transmission spectrum of a hydrated Akreos® IOL withoutphotosensitizer;

FIG. 8B is a transmission spectrum of a hydrated Akreos® IOL doped witha solution containing 17 wt. % coumarin-1;

FIG. 9A is phase contrast photograph of a hydrated Akreos® IOL withoutphotosensitizer micromachined at a scan rate of 50 μm/s and 160 mWaverage power;

FIG. 9B is phase contrast photograph of a hydrated Akreos® IOL dopedwith a solution containing 17 wt. % coumarin-micromachined at a scanrate of 50 μm/s and 160 mW average power;

FIG. 10A is phase contrast photograph of a hydrated Akreos® IOL dopedwith a solution containing 17 wt. % coumarin-1 micromachined at a scanrate of 1 mm/s and 160 mW average power;

FIG. 10B phase contrast photograph of a hydrated Akreos® IOL doped witha solution containing 17 wt. % coumarin-1 micromachined at a scan rateof 1 mm/s and 60 mW average power.

FIG. 11A is a transmission spectrum of a hydrated Pure Vision® siliconehydrogel without photosensitizer;

FIG. 11B is a transmission spectrum of a hydrated Pure Vision® siliconehydrogel doped with 0.17 wt. % fluorescein;

FIG. 12A is phase contrast photograph of a hydrated Pure Vision®silicone hydrogel without photosensitizer micromachined at a scan rateof 0.5 μm/s and 60 mW average power;

FIG. 12B is phase contrast photograph of a hydrated Pure Vision®silicone hydrogel doped with 0.17 wt. % fluorescein micromachined at ascan rate of 5.0 μm/s and 60 mW average power;

FIG. 13 is a plot of change in refractive index vs. scan rate inbalafilcon A films (undoped and doped with fluorescein and coumarin-1;

FIG. 14 are the transmission spectra of the hydrogel materials ofExample 5;

FIG. 15 is a plot of the measured change in refractive index atdifferent scan rates for the hydrogel materials of Example 5;

FIGS. 16A and 16B are plots of the measured change in refractive indexat various wavelengths at average pulse energies of 1.5 nJ and 2 nJ,respectively, for the hydrogel materials of Examples 5A and 5E;

FIG. 17 is a plot of the measured change in refractive index at variouswavelengths, an average pulse energy of 1.5 nJ and a scan rate of 1 mm/sfor the hydrogel materials of Examples 5A and 5E;

FIG. 18 is a plot of the measured change in refractive index forhydrogel materials with variable water content;

FIG. 19 is a plot of the measured change in refractive index at variouswavelengths for hydrogel materials with variable water content;

FIG. 20 is a graph showing change in index of refraction change (Δn)(vertical axis) vs. scanning speed (horizontal axis) for Akreos®-typehydrogel with 2% X-monomer in BBS at 370 mw average power at 800 nm with100 fs laser pulses at 82 MHz repetition rate;

FIG. 21 shows a cross sectional schematic view of overlapping gradientindex layers written into an optical polymeric material;

FIG. 22 shows a schematic view of multiple scan lines in a GRIN layerwhere each line is approximately two microns wide and the line spacingis one micron, according to an illustrative embodiment of the invention;

FIG. 23A is a graphical representation of gradient index profiles ofselected scan segments along the x-axis of GRIN layer 605-1 of FIG. 22;

FIG. 23B is a graphical representation of a gradient index profile of ofGRIN layer 605-1 along the y-axis of FIG. 22;

FIG. 24 is a graphical representation of a gradient index profile of aGRIN layer along an axis transverse to the scan direction that could beused to provide a negative dioptic power correction to an opticalpolymeric material;

FIG. 25A is a graphical representation of a gradient index profile of asegment of a GRIN layer as the segment is written;

FIG. 25B is a graphical representation of another gradient index profileof a segment of a GRIN layer as the segment is written;

FIG. 25C is a graphical representation of another gradient index profileof a segment of a GRIN layer as the segment is written;

FIG. 26 A is graphical representation of a gradient index profile of aGRIN layer along an axis transverse to the scan direction;

FIG. 26 B is graphical representation of another gradient index profileof a GRIN layer along an axis transverse to the scan direction;

FIG. 26 C is a graphical representation of another gradient indexprofile of a GRIN layer along an axis transverse to the scan direction;

FIG. 27A shows a Twyman Green interferogram of a one dimensionalquadratic gradient index device that is 1.8 mm wide by 4 mm long(rectangle) written in Akreos:X monomer (curved line segments showquadratic phasefronts), according to an illustrative embodiment of theinvention;

FIG. 27B is a schematic representation of the Twyman Green interferogramof FIG. 27A;

FIG. 28 shows a schematic view of an adaptive optic galvo-scanningsystem with real-time focusing feedback, according to an illustrativeembodiment of the invention;

FIG. 29 shows a schematic view of a single layer gradient indexstructure written in an optical polymeric material, according to anillustrative aspect of the invention;

FIG. 30 shows a schematic view of a three layer gradient index structurewritten in an optical polymeric material, according to an illustrativeaspect of the invention;

FIG. 31A shows two-dimensional, single GRIN layer written inThiol-ene:ITX with a galvo controlled system, according to anillustrative aspect of the invention; and

FIG. 31B is a schematic representation of the GRIN layer of FIG. 31A.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS OF THE INVENTION

If very short laser pulses of sufficient energy are used to irradiate anoptical, polymeric material, the intensity of light within the focalvolume will cause a nonlinear absorption of photons (typicallymulti-photon absorption) and lead to a change in the refractive index ofthe material within the focal volume. Moreover, the material justoutside of the focal volume will be minimally affected by the laserlight. The femtosecond laser pulse sequence pertaining to anillustrative embodied invention operates at a high repetition-rate,e.g., 80 MHz, and consequently the thermal diffusion time (>0.1 μs) ismuch longer than the time interval between adjacent laser pulses (˜11ns). Under such conditions, absorbed laser energy can accumulate withinthe focal volume and increase the local temperature. This thermalmechanism likely plays a role in the formation of laser-inducedrefractive structures in optical, polymeric materials. Moreover, thepresence of water in the polymeric material is believed toadvantageously influence the formation of the refractive structures. Assuch, optical hydrogel polymers provide much greater processingflexibility in the formation of the refractive structures as compared tozero or low water content optical polymers, e.g., the hydrophobicacrylates or low-water (1% to 5% water content) acrylate materials.

The method comprises irradiating select regions of an optical polymericmaterial such as, e.g., an optical hydrogel material, with a laser. Theirradiated regions exhibit little or no scattering loss, which meansthat the resulting refractive structures that form in the focal volumeare not clearly visible under appropriate magnification without phasecontrast enhancement. In other words, the refractive structures arevirtually transparent to the human eye without some form of imageenhancement. An optical material is a polymeric material that permitsthe transmissions of at least 80% of visible light through the material,that is, an optical material does not appreciably scatter or blockvisible light.

An exemplary method may be more advantageously carried out if an opticalpolymeric material, such as, e.g., an optical hydrogel material,includes a photosensitizer. The presence of the photosensitizer permitsone to set a scan rate to a value that is at least fifty times greater,or at least 100 times greater, than a scan rate without aphotosensitizer present in the material, and yet provide similarrefractive structures in terms of the observed change in refractiveindex of the material in the focal volume. Alternatively, thephotosensitizer in the polymeric material permits one to set an averagelaser power to a value that is at least two times less, moreparticularly up to four times less, than an average laser power withouta photosensitizer in the material, yet provide similar refractivestructures. We believe that a photosensitizer having a chromophore witha relatively large multi-photon absorption cross section captures thelight radiation (photons) with greater efficiency and then transfersthat energy to the optical polymeric material within the focal volume.The transferred energy leads to the formation of the refractivestructures and the observed change in the refractive index of thematerial in the focal volume.

In addition, Applicants previously investigated whether the formedrefractive structures resulting from the described two-photon processled to significant chemical changes, in terms of the breaking or formingof chemical bonds, in the hydrogel polymeric materials, See, U.S. Pat.No. 7,789,910, the disclosure of which is incorporated herein byreference. Applicants were quite surprised to find little or nodifference in the Raman spectrum between regions of the polymericmaterials that were exposed to the laser pulses and those regions thatwere not exposed. Typically, Raman spectroscopy is used to provideinformation on the structural or molecular changes that occur inmaterials. In the Raman scattering experiments, the hydrogel polymersamples were placed in a confocal micro-Raman spectrometer equipped withan X-Y scan stage with nanometer resolution. A 632.8 nm He—Ne laser wasfocused on the surface of the material in order to obtain the Ramanscattering signal. Due to the difference between the refractive indicesof the bulk and the irradiated regions, the scattered light at theinterface was monitored in order to ensure the laser focus was locatedin the irradiated region. A comparison of the two spectra stronglysuggests that there is no significant structural or chemical changebetween the irradiated regions and the base material.

The above Raman results were surprising in light of recent Raman spectraanalysis of fused silica modified by femtosecond laser pulses. See, J.W. Chan, T. Huser, S. Risbud, D. M. Krol, in “Structural changes infused silica after exposure to focused femtosecond laser pulses,” Opt.Lett. 26, 1726-1728 (2001). The results of Applicants Raman experiments,however, may explain why one does not observe any light scattering bythe irradiated regions (refractive structures) in the polymeric hydrogelmaterials. The Raman spectra also suggest that low pulse energy,femtosecond irradiation of optical, hydrogel materials do not causestrong structural changes in the materials even when the change of therefractive index is much higher than that obtained for fused silica.

To date, we have used a 60× 0.70NA Olympus LUCPlanFLNlong-working-distance microscope objective with variable sphericalaberration compensation. As indicated by the following equation

${\Delta\;{T\left( {r,z,{t = 0}} \right)}} = \frac{\beta\;{\tau_{P}\left\lbrack {I\left( {0,0} \right)} \right\rbrack}^{2}{\exp\left\lbrack {{- 4}\left( {\frac{r^{2}}{a^{2}} + \frac{z^{2}}{b^{2}}} \right)} \right\rbrack}}{c_{p}\rho}$the localized instantaneous temperature depends on both the pulseintensity and the magnitude of the two-photon absorption (TPA)coefficient. In order to produce an optical modification of a materialthat is of purely refractive character, i.e., non-absorbing orscattering, it is important to avoid optical damage, i.e., observedburning (scorching) or carbonization of the polymeric material. Suchmaterial or optical damage can be caused by excitation intensitiesexceeding a critical free-electron density. For hydrogel polymerscontaining a fair amount of water, the optical breakdown threshold ismuch lower than that in silica glasses. This breakdown threshold limitsthe pulse energy (in many cases to approximately 0.1 nJ to 20 nJ) thatthe hydrogel polymers can tolerate, and yet provide the observed changesin the refractive index within the focal volume.

The irradiation process and conditions described herein are verydifferent from what has been reported in femtosecond lasermicromachining studies in silica, in which much larger pulse energiesand a much larger temperature increase (several thousand Kelvin) havebeen observed. See, S. M. Eaton et al. in “Heat accumulation effects infemtosecond laser-written waveguides with variable repetition rate,”Opt. Express 2005, 13, 4708-16. Also, the specific heat constant C_(p)of water is much larger than that of silica glass (C_(P)=840 JK⁻¹kg⁻¹)and, therefore, the presence of water in the hydrogel polymeric materialis believed to moderate the temperature increase in the focal volume.

Another way to increase energy absorption at a given intensity level isto increase the nonlinear absorption coefficient β by doping theoptical, polymeric material with a particular chromophore and tuning theshort pulse laser near a two-photon transition of the chromophore. Inthis regard, we have prepared optical, hydrogel materials doped with anon-polymerizable photosensitizer or a polymerizable photosensitizer.The photosensitizer will include a chromophore having a two-photon,absorption cross-section of at least 10 GM between a laser wavelengthrange of 750 nm to 1100 nm. In the former case of a non-polymerizablephotosensitizer, we prepared solutions containing a photosensitizer andallowed the optical, hydrogel polymeric materials to come in contactwith such solutions to allow up-take of the photosensitizer into thepolymeric matrix of the polymer. In the later case of a polymerizablephotosensitizer, we used monomers containing a chromophore, e.g., afluorescein-based monomer, in the monomer mixture such that thechromophore becomes part of the polymeric matrix.

One of ordinary skill would recognize that one could easily use asolution containing a non-polymerizable photosensitizer to dope anoptical, polymeric material that had been prepared with a polymerizablephotosensitizer. Also, it is to be understood that the chromophoricentities could be the same or different in each respectivephoosensitizer.

Our studies have shown that by doping the hydrogel material with thephotosensitizer either by solution doping or by using a polymerizablephotosensitizer, the localized temperature increase can reach atransition point of the polymer; the goal being to reach this transitionpoint to provide a desired change in the refraction index, yet maintaina safe margin of intensity below the damage threshold level of thehydrogel material.

It is also important to note that the photosensitizer relied upon byApplicants to increase the photoefficiency of the two-photon process,and thereby, increase the photoefficiency of making the refractivestructures resulting in the observed change in the refractive index ofthe polymeric hydrogel materials, does not undergo significantstructural or chemical transformation in the process. Again, no changesin the Raman spectra of photosentized polymeric materials is observedbetween the irradiated and non-irradiated regions. This is consistentwith the order of magnitude(s) increase in the observed efficiency forforming the refractive structures with material doped with aphotosensitizer. For example, Applicants have observed an increase inthe efficiency of forming the refractive structures by 100-fold or moresimply by doping a given hydrogel material with 0.17 wt. % of apolymerizable monomer having a chromophore necessary forphotosensitization. This very small concentration of dopedphotosensitizer cannot by itself account for the observed increase inefficiency.

The concentration of a polymerizable, monomeric photosensitizer having atwo-photon, chromophore in an optical material, preferably an optical,hydrogel material, can be as low as 0.05 wt. % and as high as 10 wt. %.Exemplary concentration ranges of polymerizable monomer having atwo-photon, chromophore in an optical, hydrogel material is from 0.1 wt.% to 6 wt. %, 0.1 wt. % to 4 wt. %, and 0.2 wt. % to 3 wt. %. In variousaspects, the concentration range of polymerizable monomerphotosensitizer having a two-photon, chromophore in an optical, hydrogelmaterial is from 0.4 wt. % to 2.5 wt. %.

Due to the high repetition rate pulse sequence used in the irradiationprocess, the accumulated focal temperature increase can be much largerthan the temperature increase induced by a single laser pulse. Theaccumulated temperature increases until the absorbed power and thedissipated power are in dynamic balance. For hydrogel polymers,thermal-induced additional crosslinking within the polymer network canproduce a change in the refractive index as the local temperatureexceeds a transition temperature. If the temperature increase exceeds asecond threshold, a somewhat higher temperature than the transitiontemperature, the polymer is pyrolytically degraded and carbonizedresidue and water bubbles are observed. In other words, the materialexhibits visible optical damage (scorching). As a result of ourinvestigations described herein, each of the following experimentalparameters such as laser repetition rate, laser wavelength and pulseenergy, TPA coefficient, and water concentration of the materials shouldbe considered so that a desired change in the refractive index can beinduced in the hydrogel polymers without optical damage.

The pulse energy and the average power of the laser, and the rate atwhich the irradiated regions are scanned, will in-part depend on thetype of polymeric material that is being irradiated, how much of achange in refractive index is desired and the type of refractivestructures one wants to create within the material. The selected pulseenergy will also depend upon the scan rate and the average power of thelaser at which the refractive structures are written into the polymermaterial. Typically, greater pulse energies will be needed for greaterscan rates and lower laser power. For example, some materials will callfor a pulse energy from 0.05 nJ to 100 nJ or from 0.2 nJ to 10 nJ.

Within the stated pulse energies above, the optical, hydrogel polymericmaterial is irradiated at a scan rate of at least 0.1 mm/s, from 0.1mm/s to 10 mm/s or from 0.4 mm/s to 4 mm/s.

Within the stated pulse energies and scan rates above, the average laserpower used in the irradiation process is from 10 mW to 400 mW, or from40 mW to 220 mW.

In one aspect, the average pulse energy is from 0.2 nJ to 10 nJ and theaverage laser power is from 40 mW to 220 mW. The laser also operateswithin a wavelength of 650 nm to 950 nm. Within the stated laseroperating powers, the optical, hydrogel polymeric material is irradiatedat a scan rate from 0.4 mm/s to 4 mm/s.

A photosensitizer will include a chromophore in which there is little orno intrinsic linear absorption in the spectral range of 600-1000 nm. Thephotosensitizer is present in the optical, hydrogel polymeric materialto enhance the photoeffiency of the two-photon absorption required forthe formation of the described refractive structures. Photosensitizersof particular interest include, but are not limited to, the followingcompounds. The compounds below are merely exemplary.

As is described in greater detail in the Example section, a commercialIOL material, Akreos®, presently marketed by Bausch & Lomb, wassubjected to laser irradiation according to the processes describedherein. An Akreos® IOL is a HEMA-based, hydrogel material with 26% to28% water content. The micromachining process was used to imprintrefractive structures in an Akreos® IOL without photosensitizer and anAkreos® IOL doped with a solution containing 17 wt. % cormarin-1. Theirradiation experiments were conducted with both dry and hydratedmaterials. The refractive structures formed only in the hydratedmaterials.

In brief, the magnitude of the measured change in refractive index wasat least ten times greater in the Akreos® IOL doped with the coumarinsolution at a given scan rate and an average laser power than theAkreos® IOL without the coumarin. Surprisingly, an increase in scan rateto 1 mm/s at an average laser power of 160 mW provided refractivestructures with a change in refractive index of 0.02 to 0.03. Moreover,reducing the laser power to 60 mW still provided refractive structureswith a change in refractive index of about 0.005.

In another illustrative aspect, a balafilcon A silicone hydrogel wasprepared by adding fluorescein monomer (0.17% by weight) as apolymerizable photosensitizer to the polymer monomer mixture. Thebalafilcon A doped with fluorescein was then subjected to laserradiation according to the processes described herein. Again, thedescribed irradiation process was used to imprint refractive structuresin the silicone hydrogel without photosensitizer and the siliconehydrogel doped with 0.17 wt. % fluorescein monomer. Again, experimentswere conducted with both dry and hydrated materials, and again, therefractive structures formed only in the hydrated materials. In brief,the magnitude of the measured change in refractive index was at leastten times greater in the balafilcon A silicone hydrogel doped with 0.17wt. % fluorescein monomer at an average laser power of 60 mW thanbalafilcon A without the photosensitizer. This 10-fold difference inchange in refractive index was observed even with a 10-fold increase inscan rate in the photosensitized material; i.e., 0.5 mm/s in the undopedmaterial and 5.0 mm/s in the photosensitized material.

In some cases, the formation of refractive structures as describedrequires that the pulse width be preserved so that the pulse peak poweris strong enough to exceed the nonlinear absorption threshold of theoptical polymeric material. However, the glass of the focusingobjective(s) significantly increases the pulse width due to the positivedispersion of the glass. A compensation scheme is used to provide acorresponding negative dispersion that can compensate for the positivedispersion introduced by the focusing objective(s). Accordingly, acompensation scheme can be used to correct for the positive dispersionintroduced by the focusing objective(s). The compensation scheme caninclude an optical arrangement selected from the group consisting of atleast two prisms and at least one mirror, at least two diffractiongratings, a chirped mirror and dispersion compensating mirrors tocompensate for the positive dispersion introduced by the focusobjective.

In different aspects, the compensation scheme included at least oneprism, in many cases at least two prisms, and at least one mirror tocompensate for the positive dispersion of the focusing objective. Inanother aspect, the compensation scheme included at least two gratingsto compensate for the positive dispersion of the focusing objective. Anyappropriate combination of prisms, gratings and/or mirrors can be usedfor the compensation scheme.

The laser will generate light with a wavelength in the range from violetto near-infrared. In various aspects, the wavelength of the laser is inthe range from 400 nm to 1500 nm, from 400 nm to 1200 nm, or from 650 nmto 950 nm.

In an exemplary aspect, the laser is a pumped Ti:sapphire laser with anaverage power of 10 mW to 1000 mW. Such a laser system will generatelight with a wavelength of approximately 800 nm. In another exemplaryaspect, an amplified fiber laser that can generate light with awavelength from 1000 nm to 1600 nm may be used.

The laser will have a peak intensity at focus of greater than 10¹³W/cm². At times, it may be advantageous to provide a laser with a peakintensity at focus of greater than 10¹⁴ W/cm², or greater than 10¹⁵W/cm².

The ability to form refractive structures in optical polymeric materialsprovides an important opportunity to an ophthalmic surgeon orpractitioner to modify the refractive index of an optical device, e.g.,an intraocular lens or corneal inlay, following implantation of thedevice into an eye of a patient. The method allows the surgeon tocorrect aberrations as a result of the surgery. The method also allowsthe surgeon to adjust the refractive properties of the lens or inlay byadjusting the refractive index in the irradiated regions based on thevision correction required of each patient. For example, starting from alens of selected power (will vary according to the ocular requirementsof the patient), the surgeon can further adjust the refractiveproperties of the lens to correct a patient's vision based upon theindividual needs of the patient. In essence, an intraocular lens wouldessentially function like a contact lens or glasses to individuallycorrect for the refractive error of a patient's eye. Moreover, becausethe implanted lens can be adjusted by adjusting the refractive index ofselect regions of the lens, post-operative refractive errors resultingfrom pre-operative measurement errors, variable lens positioning duringimplantation, and wound healing (aberrations) can be corrected or finetuned in-situ.

For instance, cataract surgery typically requires that the natural lensof each eye be replaced with an IOL. Following insertion of the IOL, thesurgeon can correct for aberrations resulting from the surgery orcorrect for slight misplacement of the IOL. Following surgery, and afterallowing time for the wound to heal, the patient would return to thesurgeon or an ophthalmic practitioner to have select regions of the IOLirradiated. These irradiated regions would experience a positive changein refractive index, which would correct for the aberrations as well asthe patient's needs for vision correction. In some instances, thesurgeon would be able to adjust the IOL in one eye for distance andadjust the IOL in the opposite eye for reading.

Typically, the irradiated portions of the optical, hydrogel polymericmaterial will exhibit a positive change in refractive index of about0.01 or more. In one embodiment, the refractive index of the region willincrease by about 0.03 or more. We have measured a positive change inrefractive index in a hydrated, Akreos® IOL material of about 0.06.

It is to be understood by one of ordinary skill in the art, that anembodied method modifies the refractive properties of the material notby casting an optical material with non-reacted monomer (refractionmodulation composition) followed by laser irradiation to promoteadditional polymerization chemistry as described in the aforementionedCalhoun Patent, but rather by a change in the refractive index of analready completely polymerized optical material. The term “completelypolymerized” when used to characterize the optical materials used in thedisclosed method means that the optical materials are 95% or morepolymerized. One way to measure the completeness of a polymerizedoptical material is by near infra-red spectroscopy, which is used toqualitatively determine the vinyl content of the material. Simplegravimetric weight analysis can also be used.

In an exemplary aspect, the irradiated regions of the optical, polymericmaterial can be defined by two- or three-dimensional structures. Thetwo- or three-dimensional structures can comprise an array of discretecylinders. Alternatively, the two- or three-dimensional structures cancomprise a series of lines, or a combination of an array of cylindersand a series of lines. Moreover, the two- or three-dimensionalstructures can comprise area or volume filled structures, respectively.These area or volume filled structures can be formed by continuouslyscanning the laser at a constant scan rate over a selected region of thepolymeric material. Nanometer-sized structures can also be formed by thezone-plate-array lithography method describe by R. Menon et al., Proc.SPIE, Vol. 5751, 330-339 (May 2005); Materials Today, p. 26 (February2005).

In one embodiment, the irradiated regions of the optical polymer aredefined by a series of line segments in a two dimensional plane having aline width from 0.2 μm to 5 μm, more particularly a line width from 0.6μm to 3 μm and a height from 0.4 μm to 8 μm, more particularly a heightfrom 1.0 μm to 4 μm (height is measured in the z direction of thematerial, which is parallel to direction of the laser light). Forexample, one can generate a segment array comprising a plurality of linesegments with each line segment of any desired length, about 0.8 μm toabout 3 μm in width and about 2 μm to 5 μm in height. The line segmentscan be separated by as little as 1.0 μm (0.5 μm spacing), and any numberof line segments can be incorporated into the material. Moreover, thesegment array can be positioned at any selected depth (z-direction), andany number of segment arrays can be generated at various depths into thematerial.

FIG. 1A is a microscope photograph with contrasting background of a linesegment array comprising 20 lines written into an optical material. FIG.1B is a schematic representation of the microscope photograph of FIG.1A. Each line segment is about 100 μm in length, about 1 μm in width,with an intersegment separation of about 5 μm. The line segments have aheight of about 3 μm and were written into the material at a distance ofabout 100 μm from the top surface of the material. Similar microscopephotographs exhibiting line segment arrays were obtained at a distanceof about 200 μm and 400 μm from the top surface of the material, therebydemonstrating that refractive structures can be written into the opticalmaterial at any selected depth.

FIG. 2A is a microscopic photograph with contrasting background of onesegment array written above and orthogonal to another segment array.FIG. 2B is a schematic representation of the microscope photograph ofFIG. 2A. Each of the arrays has a similar dimensional structure to thatdescribed for FIG. 1 above. One segment array is positioned about 100 μminto the material, and the other segment array is positioned about 110μm into the material for a center-line, segment array separation ofabout 10 μm. Again, each of these segment arrays has a height (depth) ofabout 3 μm, thus providing an intersegment separation in z of about 7μm.

FIG. 3A is a microscopic photograph with contrasting background of anarray of cylinders written into an optical material. FIG. 3B is aschematic representation of the microscope photograph of FIG. 3A. Eachcylinder is about 1 μm in diameter with a height of about 3 μm. Thecylinders are separated by about 5 μm. The cylinders were laser-etchedinto the material at a distance of about 100 μm from the top surface ofthe material.

FIG. 4A is a microscopic photograph with contrasting background of onearray of cylinders (20×20) written above and slightly offset to anotherarray of cylinders (20×20). FIG. 4B is a schematic representation of themicroscope photograph of FIG. 4A. Each of the cylinders has a similardimensional structure to that described for FIG. 3 above. One array ispositioned about 100 μm into the material, and the other array ispositioned about 105 μm into the material for a center-line separationof about 5 μm. Each of the cylinders has a height (depth) of about 3 μm.

The area-filled or volume-filled two- or three-dimensional structurescan be formed by continuously scanning the laser at a constant scan rateover selected regions of the optical, polymeric material. As described,refractive structures can be written within the volume of an opticalpolymer material by repeatedly scanning a tightly focused beam offemtosecond pulses in selected regions creating a plurality of linesegments. The volume of a line segment can be changed correspondinglywith the depth of the scan, so as to produce three-dimensionally-shapedlenses with spheric, aspheric, toroidal or cylindrical shapes as shownin FIG. 5. Although the refractive index change is positive (+0.02 to+0.06), these refractive corrective lenses can be made in variouscombinations of convex, plano-, or concave to yield a positivecorrection or negative correction, as shown in FIG. 6. The refractivestructures can be stacked vertically, written separately in differentplanes, so as to act as a single lens element. Additional refractivestructures can be written as desired.

As indicated by the micrographs of the refractive structures describedas area-filled or volume-filled two- or three-dimensional structures,one can create a pattern of lines, cylinders and radial patterns inoptical materials; however, it is also possible to create other opticalfeatures using the irradiation method described herein. For example,arrays of dots (e.g., having a dimension in the nanometer range) can becreated by directing the laser beam at discrete points or spots withinthe material. Such an array can be arranged substantially on one planeor several such arrays can be created at different depths within thematerial. A material thus modified can be advantageously useful whenlight is not substantially scattered by the dots.

In one aspect, the refractive structures are formed proximate to the topanterior surface of an intraocular lens. For example, a positive ornegative lens element (three-dimensional) is formed within a 300 μmvolume, or within a 100 μm volume, from the anterior surface of thelens. The term “anterior surface” is the surface of the lens that facesthe anterior chamber of a human eye.

A Laser and Optical Configuration for Modifying an Optical Material

A non-limiting embodiment of a laser system 10 for irradiating anoptical, polymeric material with a laser to modify the refractive indexof the material in select regions is illustrated in FIG. 7. A lasersource comprises a Kerr-lens mode-locked Ti:Sapphire laser 12(Kapteyn-Murnane Labs, Boulder, Colo.) pumped by 4 W of afrequency-doubled Nd:YVO4 laser 14. The laser generates pulses of 300 mWaverage power, 30 fs pulse width, and 93 MHz repetition rate atwavelength of 800 nm. Because there is a reflective power loss from themirrors and prisms in the optical path, and in particular from the powerloss of the objective 20, the measured average laser power at theobjective focus on the material is about 120 mW, which indicates thepulse energy for the femtosecond laser is about 1.3 nJ.

Due to the limited laser pulse energy at the objective focus, the pulsewidth must be preserved so that the pulse peak power is strong enough toexceed the nonlinear absorption threshold of the materials. Because alarge amount of glass inside the focusing objective significantlyincreases the pulse width due to the positive dispersion inside of theglass, an extra-cavity compensation scheme is used to provide thenegative dispersion that compensates for the positive dispersionintroduced by the focusing objective. Two SF10 prisms 24 and 28 and oneending mirror 32 form a two-pass, one-prism-pair configuration. In aparticular instance, Applicants used a 37.5 cm separation distancebetween the prisms to compensate for the positive dispersion of themicroscope objective and other optics within the optical path.

A collinear autocorrelator 40 using third-order harmonic generation isused to measure the pulse width at the objective focus. Both 2^(nd) and3^(rd) harmonic generation have been used in autocorrelationmeasurements for low NA or high NA objectives. Applicants also selectedthird-order surface harmonic generation (THG) autocorrelation tocharacterize the pulse width at the focus of the high-numerical aperture(NA) objectives because of its simplicity, high signal to noise ratio,and lack of material dispersion that second harmonic generation (SHG)crystals usually introduce. The THG signal is generated at the interfaceof air and an ordinary cover slip 42 (Corning No. 0211 Zinc Titaniaglass), and measured with a photomultiplier 44 and a lock-in amplifier46. After using a set of different high-numerical-aperture objectivesand carefully adjusting the separation distance between the two prismsand the amount of glass inserted, a transform-limited 27 fs durationpulse is used, which is focused by a 60× 0.70NA Olympus LUCPlanFLNlong-working-distance objective 48.

Because the laser beam will spatially diverge after it comes out of thelaser, a concave mirror pair 50 and 52 is added into the optical path inorder to adjust the dimension of the laser beam so that the laser beamcan optimally fill the objective aperture. A 3D 100 nm resolution DCservo motor stage 54 (Newport VP-25XA linear stage) and a 2D 0.7 nmresolution piezo nanopositioning stage (PI P-622.2CD piezo stage) arecontrolled and programmed by a computer 56 as a scanning platform tosupport and locate the samples. The servo stages have a DC servo-motorso they can move smoothly between adjacent steps. An optical shuttercontrolled by the computer with 1 ms time resolution is installed in thesystem to precisely control the laser exposure time. With customizedcomputer programs, the optical shutter could be operated with thescanning stages to micromachine different patterns in the materialsusing different scanning speeds at different position or depth in theoptical material, and different laser exposure times. In addition, a CCDcamera 58 along with a monitor 62 is used beside the objective 20 tomonitor the process in real time.

The method and optical apparatus described above can be used to modifythe refractive index of an intraocular lens following the surgicalimplantation of the intraocular lens in a human eye (or before the lensis implanted in an eye).

Accordingly, an embodiment of the invention is directed to a methodcomprising identifying and measuring the aberrations resulting from thesurgical procedure of providing a patient with an IOL. Once theaberrations are identified and quantified using methods well known inthe art of ophthalmology, this information is processed by a computer.Of course, information related to the requisite vision correction foreach patient can also be identified and determined, and this informationcan also be processed by a computer. There are a number of commerciallyavailable diagnostic systems that are used to measure the aberrations.For example, common wavefront sensors used today are based on theSchemers disk, the Shack Hartmann wavefront sensor, the Hartmann screen,and the Fizeau, and Twyman-Green interferometers. The Shack-Hartmannwavefront measurement system is known in the art and is describedin-part by U.S. Pat. Nos. 5,849,006; 6,261,220; 6,271,914 and 6,270,221.Such systems operate by illuminating a retina of the eye and measuringthe reflected wavefront.

Once the aberrations are identified and quantified, the computerprograms determine the position and shape of the refractive structuresto be written into the lens material to correct for those aberrations orto provide vision correction to the patient. These computer programs arewell known to those of ordinary skill in the art. The computer thencommunicates with the laser-optical system and select regions of thelens are irradiated with a laser having a pulse energy from 0.05 nJ to1000 nJ as described herein.

The Optical, Hydrogel Polymeric Materials

The optical, hydrogel polymeric materials that can be irradiated with alaser according to the methods described in this application can be anyoptical, hydrogel polymeric material known to those of ordinary skill inthe polymeric lens art, particularly those in the art familiar withoptical polymeric materials used to make intraocular lenses.Non-limiting examples of such materials include those used in themanufacture of ophthalmic devices, such as siloxy-containing polymers,acrylic, hydrophilic or hydrophobic polymers or copolymers thereof. Theforming of the refractive structures is particularly suited formodifying the refractive index in select and distinct regions of apolymeric, optical silicone hydrogel, or a polymeric, opticalnon-silicone hydrogel.

The term “hydrogel” refers to an optical, polymeric material that canabsorb greater than 10% by weight water based on the total hydratedweight. In fact, many of the optical, hydrogel polymeric materials willhave a water content greater than 15% or greater than 20%. For example,many of the optical, hydrogel polymeric materials will have a watercontent from 15% to 60% or from 15% to 40%.

The optical, hydrogel polymeric materials are of sufficient opticalclarity, and will have a relatively high refractive index ofapproximately 1.40 or greater, particularly 1.48 or greater. Many ofthese materials are also characterized by a relatively high elongationof approximately 80 percent or greater.

In one embodiment, the optical polymeric materials are prepared as acopolymer from at least three monomeric components. The first monomericcomponent, preferably a monomeric component with aromatic functionality,is present in the copolymer in an amount of at least 60% by weight, andits homopolymer will have a refractive index of at least 1.50,particularly at least 1.52 or at least 1.54. The second monomericcomponent, preferably, an alkyl(meth)acrylate, is present in thecopolymer in an amount from 3% to 20% or from 3% to 10%, by weight. Thefirst and second monomeric components together represent at least 70% byweight of the copolymer. The term “homopolymer” refers to a polymer thatis derived substantially completely from the respective monomericcomponent. Minor amounts of catalysts, initiators, and the like can beincluded, as is conventionally the case, in order to facilitate theformation of the homopolymer.

Particularly useful first monomeric components include styrene, vinylcarbazole, vinyl naphthalene, benzyl(meth)acrylate,phenyl(meth)acrylate, naphthyl(meth)acrylate,2-phenoxyethyl(meth)acrylate, 2,3-dibromopropyl-(meth)acrylate and anyone mixture thereof. Particularly useful second monomeric componentsinclude n-butyl(meth)acrylate, n-hexyl(meth)acrylate,2-ethylhexyl-(meth)acrylate, 2-ethoxyethyl(meth)acrylate,2,3-dibromopropyl(meth)acrylate, 1,1-dihydroperfluorobutyl(meth)acrylateand any one mixture thereof.

The third monomeric component is a hydrophilic monomeric component. Thehydrophilic component is present in an amount, from 2% to 30% by weightof the copolymer. The hydrophilic component is particularly present inan amount of less than about 20% by weight of the copolymer. Copolymersthat include about 10% by weight or more of a hydrophilic monomericcomponent tend to form hydrogels if placed in an aqueous environment.The term “hydrophilic monomeric component” refers to compounds thatproduce hydrogel-forming homopolymers, that is, homopolymers whichbecome associated with at least 25% of water, based on the weight of thehomopolymer, if placed in contact with an aqueous solution.

Specific examples of useful hydrophilic monomeric components includeN-vinyl pyrrolidone; hydroxyalkyl (meth)acrylates such as 2-hydroxyethyl(meth)acrylate, 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl(meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2,3-dihydroxypropyl(meth)acrylate and the like; acrylamide; N-alkyl acrylamides such asN-methyl acrylamide, N-ethyl acrylamide, N-propyl acrylamide, N-butylacrylamide and the like; acrylic acid; methacrylic acid; and the likeand any one mixture thereof.

In another embodiment, the optical polymeric materials are prepared as acopolymer from at least two monomeric components and a photosensitizer.The photosensitizer can be polymerizable or be entrapped within theformed polymer. The first monomeric component is a hydrophilic monomericcomponent. The hydrophilic component is present in an amount from 50% to90% by weight of the copolymer. The hydrophilic component isparticularly present in an amount of 60% to 85% by weight of thecopolymer. The second monomeric component, preferably, analkyl(meth)acrylate, is present in the copolymer in an amount from 5% to20% or from 3% to 10%, by weight. The first and second monomericcomponents together represent at least 90% by weight of the copolymer.

The polymeric optical materials will likely include a crosslinkcomponent that can form crosslinks with at least the first or the secondmonomeric components. Advantageously, the crosslink component ismulti-functional and can chemically react with both the first and secondmonomeric components. The crosslink component is often present in aminor amount relative to the amounts of the first and second monomericcomponents. Particularly, the crosslink component is present in acopolymer in an amount of less than about 1% by weight of the copolymer.Examples of useful crosslink components include ethylene glycoldimethacrylate, propylene glycol dimethacrylate, ethylene glycoldiacrylate and the like and mixtures thereof.

In one aspect, the optical, polymeric materials can be prepared from oneor more aromatic (meth)acrylate monomers having the formula:

wherein: R is H or CH₃; m is an integer selected from 0 to 10; Y isnothing, 0, S, or NR¹, wherein R¹ is H, CH₃, C₂-C₆alkyl, iso-OC₃H₇,phenyl or benzyl; Ar is any aromatic ring, e.g., phenyl, which can beunsubstituted or substituted with H, CH₃, C₂H₅, n-C₃H₇, iso-C₃H₇, OCH₃,C₆H₁₁, Cl, Br, phenyl or benzyl; and a crosslinking component.

Exemplary aromatic (meth)acrylate monomers include, but are not limitedto: 2-ethylphenoxy (meth)acrylate, 2-ethylthiophenyl (meth)acrylate,2-ethylaminophenyl (meth)acrylate, phenyl-(meth)acrylate, benzyl(meth)acrylate, 2-phenylethyl (meth)acrylate,3-phenylpropyl-(meth)acrylate, 4-phenylbutyl (meth)acrylate,4-methylphenyl (meth)acrylate, 4-methylbenzyl (meth)acrylate,2-2-methylphenylethyl (meth)acrylate, 2-3-methylphenylethyl(meth)acrylate, 2-4-methylphenylethyl (meth)acrylate,2-(4-propylphenyl)ethyl (meth)acrylate, 2-(4-(1-methylethyl)phenyl)ethylmethacrylate, 2-(4-methoxyphenyl)ethyl methacrylate and the like.

Generally, if the optical, polymeric material is prepared with both anaromatic acrylate and an aromatic methacrylate as defined by the formulaabove, the materials will generally comprise a greater mole percent ofaryl acrylate ester residues than of aryl methacrylate ester residues.It is preferred that the aryl acrylate monomers constitute from about 20mole percent to about 60 mole percent of the polymer, while the arylmethacrylate monomers constitute from about 5 mole percent to about 20mole percent of the polymer. Most advantageous is a polymer comprisingabout 30-40 mole percent 2-phenylethyl acrylate and about 10-20 molepercent 2-phenylethyl methacrylate. Hydrophilic monomer is also presentin about 20-40 mol percent.

In another aspect, the optical, polymeric materials will have a fullyhydrated (equilibrium) water content from 5% to 15% by weight, whichalso helps to minimize the degree of hazing following thermal stress asdescribed, as well as minimize the formation of water vacuoles in-vivo.To achieve the desired water content, one may include a hydrophilic,aromatic monomer having a formula, G-D-Ar, wherein Ar is a C₆-C₁₄aromatic group having a hydrophilic substituent, in the polymerizablecompositions. D is a divalent linking group, and G is a polymerizableethylenic site.

One particular hydrophilic aromatic monomer is represented by theformula

wherein R is hydrogen or CH₃; D is a divalent group selected from thegroup consisting of straight or branched C₁-C₁₀ hydrocarbons and analkyleneoxide (e.g., —(CH₂CH₂O)_(n)—), and E is selected from the groupconsisting of hydrogen (if D is alkyleneoxide), carboxy, carboxamide,and monohydric and polyhydric alcohol substituents. Exemplaryhydrophilic substituents include, but are not limited to, —COOH,—CH₂—CH₂OH, —(CHOH)₂CH₂OH, —CH₂—CHOH—CH₂OH, poly(alkylene glycol),—C(O)O—NH₂ and —C(O)—N(CH₃)₂.

Exemplary hydrophilic, aromatic monomers are represented by thefollowing

wherein R is hydrogen or CH₃ and R¹ is —C(O)O—NH₂ or —C(O)—N(CH₃)₂.

In another aspect, the optical, polymeric material is prepared from afirst aromatic monomeric component, which is present in 5-25% by weight,the second monomeric component is a hydrophilic monomeric component,e.g., 2-hydroxyethyl (meth)acrylate, which is present from 30 to 70% byweight; and 5 to 45% by weight of a another alkyl (meth)acrylateselected from the group consisting of methyl (meth)acrylate, ethyl(meth)acrylate, propyl (meth)acrylate, butyl (meth)acrylate, pentyl(meth)acrylate, hexyl meth)acrylate, heptyl (meth)acrylate, nonyl(meth)acrylate, stearyl meth)acrylate, octyl (meth)acrylate, decyl(meth)acrylate, lauryl (meth)acrylate, pentadecyl (meth)acrylate and2-ethylhexyl (meth)acrylate. Among the alkyl (meth)acrylates, thosecontaining 1 to 3 carbon atoms of alkyl group are particularlyadvantageous.

Exemplary aromatic monomeric components include ethylene glycol phenylether acrylate (EGPEA), poly(ethylene glycol phenyl ether acrylate)(polyEGPEA), phenyl methacrylate, 2-ethylphenoxy methacrylate,2-ethylphenoxy acrylate, hexylphenoxy methacrylate, hexylphenoxyacrylate, benzyl methacrylate, 2-phenylethyl methacrylate,4-methylphenyl methacrylate, 4-methylbenzyl methacrylate,2-2-methyphenylethyl methacrylate, 2-3-methylphenylethyl methacrylate,2-4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethylmethacrylate, 2-(4-(1-methylethyl)pheny)ethyl methacrylate,2-(4-methoxyphenyl)ethylmethacrylate, 2-(4-cyclohexylpheny)ethylmethacrylate, 2-(2-chlorophenyl)ethyl methacrylate,2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethylmethacrylate, 2-(4-bromophenyl)ethyl methacrylate,2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethylmethacrylate), 2-(4-benzylphenyl)ethyl methacrylate, and the like,including the corresponding methacrylates and acrylates, and includingmixtures thereof. EGPEA and polyEGPEA are two of the more preferredfirst monomeric components.

In another aspect, the optical, polymeric material is prepared from ahydrophilic acrylic that comprises about 90% (by weight)N-vinylpyrrolidone (NVP) and about 10% (by weight)4-t-butyl-2-hydroxycyclohexyl methacrylate. This methacrylate hydrogelcan absorb about 80% (by weight) water because of the high percentage ofNVP. Its refractive index when hydrated is very close to the index ofwater. Another hydrophilic acrylic of interest is referred to as HEMA B,which is a poly(2-hydroxyethyl methacrylate) cross-linked with about0.9% (by weight) of ethylene glycol dimethacrylate (“EGDMA”). ThisHEMA-hydrogel can absorb about 37% (by weight) water.

One particular hydrophilic, acrylic material of interest is based upon acommercially available IOL sold in the market by Bausch & Lomb under thetrade name Akreos®. This acrylic material comprises about 80% by weightHEMA and 20 wt % MMA.

The optical, polymeric material can also be prepared by copolymerizing aspecific monomer mixture comprising perfluorooctylethyloxypropylene(meth)acrylate, 2-phenylethyl (meth)acrylate, an alkyl (meth)acrylatemonomer having the following general formula,

wherein R is hydrogen or methyl and R¹ is a linear or branched C₄-C₁₂alkyl group, hydrophilic monomer and a crosslinking monomer. Anexemplary list of alkyl (meth)acrylate monomer include n-butyl acrylate,isobutyl acrylate, isoamyl acrylate, hexyl acrylate, 2-ethylhexylacrylate, octyl acrylate, isooctyl acrylate, decyl acrylate, isodecylacrylate, and the like.

The perfluorooctylethyloxypropylene (meth)acrylate is present from 5% to20% by weight, the 2-phenylethyl (meth)acrylate is present from 20% to40% by weight, the alkyl (meth)acrylate monomer is present from 20% to40% by weight, the hydrophilic monomer is present from 20% to 35%, andthe crosslinking agent is present from 0.5% to 2% by weight.

The optical, polymeric component will likely include a crosslinkingagent. The copolymerizable crosslinking agent(s) useful in forming thecopolymeric material of the invention include any terminallyethylenically unsaturated compound having more than one unsaturatedgroup. Particularly, the crosslinking agent includes a diacrylate or adimethacrylate. The crosslinking agent may also include compounds havingat least two (meth)acrylate and/or vinyl groups. Particularlyadvantageous crosslinking agents include diacrylate compounds.

The optical, polymeric materials are prepared by generally conventionalpolymerization methods from the respective monomeric components. Apolymerization mixture of the monomers in the selected amounts isprepared and a conventional thermal free-radical initiator is added. Themixture is introduced into a mold of suitable shape to form the opticalmaterial and the polymerization initiated by gentle heating. Typicalthermal, free radical initiators include peroxides, such as benzophenoneperoxide, peroxycarbonates, such as bis-(4-t-butulcyclohexyl)peroxydicarbonate, azonitriles, such as azobisisobytyronitrile, and thelike. A particular initiator is bis-(4-t-butylcyclohexyl)peroxydicarbonate (PERK). Alternatively, the monomers can bephotopolymerized by using a mold which is transparent to actinicradiation of a wavelength capable of initiating polymerization of theseacrylic monomers by itself. Conventional photoinitiator compounds, e.g.,a benzophenone-type photoinitiator, can also be introduced to facilitatethe polymerization.

EXAMPLES Example 1. Preparation of Akreos IOL with 17% Coumarin-1

Coumarin 1 dye (2.5 g) is dissolved in an ethanol-water mixturecontaining 10 mL ethanol and 5 mL water. Dry weight of the Akreos sampleis recorded. The samples are hydrated in pure water and the mass isrecorded. Following the hydration step, the samples are soaked in theethanol-water mixture containing the coumarin 1 dye until a constantmass is attained. The mass after soaking in the dye solution isrecorded. Mass of the dye doped is calculated as the difference betweenthe mass after soaking in the solution, and the dry mass multiplied bythe mass concentration of the dye in the ethanol-water solution.Percentage of the dye doped is calculated as the ratio of mass ofcoumarin 1 dye doped over the dry mass multiplied by 100.

Example 2. Forming Structures in Akreos IOL Materials

The optical system described herein above was used to form line segmentsin select regions of optical materials. Experiments were conducted withAkreos IOL materials with and without photosensitizer. Akreos IOLmaterials comprise about 80 wt % HEMA and 20 wt % MMA with a watercontent of about 26% using similar process conditions described above.

The hydrated sample was mounted horizontally on the scanning platform,and the femtosecond laser beam was directed vertically downward throughthe high-numerical-aperture objective and was focused inside the bulkmaterial, as shown in FIG. 7, at a depth of about 100 μm from the uppersurface of the sample. Periodic gratings structures were created with ascanning speed of 0.4 μm/sec in an X-Y plane perpendicular to the laserbeam. An Olympus BX51 Model microscope was used to observe the gratingsthat were created inside these three materials.

The microscope images indicate the formation of periodic parallel linesegments inside the samples with 5-μm spacing. The segments aredifficult to see in bright-field microscope, indicating that thesegments exhibit low scattering. The line width of the segments is about1 μm, which is significantly smaller than the laser focus diameter of2.5 μm that was measured using a knife-edge method.

A cross section of the irradiated materials revealed that the crosssection of a line segment was elliptical with the longer axis orientedin the direction of the laser beam, indicating that there was a largerlaser intensity distribution in this direction. By carefully adjustingthe cover-slip correction of the objective, this spherical aberrationcould be minimized.

As indicated in FIGS. 8A and 8B, the incorporation of coumarin-1 into anAkreos IOL provided a red shift in the transmission spectrum of anAkreos IOL material of about 50 nm. The Akreos IOL material withcoumarin-1 has a relatively significant absorption profile at 400 nm andto about 425 nm, whereas an Akreos IOL material without photosensitizeris essentially transparent at these wavelengths.

FIGS. 9A and 9B are phase contrast photographs of Akreos IOL materialswith refractive line segments written within the materials at a depth ofabout 200 μm from the top irradiated surface. The irradiation processwas conducted at 160 mW average power and a scan rate of 50 μm/s. Asindicated in FIG. 9A, the refractive line segments written in the AkreosIOL material without photosensitizer provide little, if any, change inrefractive index, Δn<<0.005 (visible detection limit of the structures).In fact, it is very difficult to see the refractive line segments in thematerial even with phase contrast enhancement. In contrast, as indicatedin FIG. 9B, the refractive line segments written in the Akreos IOLmaterial with 17% coumarin-1 at the identical power and scan rateprovide a very significant change in refractive index, Δn>0.06. The linesegments are clearly visible with phase contrast enhancement.

FIGS. 10A and 10B indicate how differences in the refractive power ofthe written line segments (the magnitude of change in refractive index)can be varied based on the constant scan rate and laser power. FIG. 10Ashows that one can form refractive line segments in Akreos IOL materialswith 17% coumarin-1 at a scan rate of 1 mm/s, and with a Δn of about0.02 to 0.3. This is a surprising result since one would have to scan atabout 10 μm/s to generate similar line segments with a Δn of about 0.02to 0.3 in an Akreos IOL material without photosensitizer. The presenceof the coumarin-1 allows one to increase the scan rate nearly 100-fold.Moreover, even with a relatively low laser power, i.e., 60 mW, one canstill generate refractive line segments with a Δn of about 0.005.

Example 3. Preparation of Pure Vision® Silicone Hydrogel with 0.07 wt. %Fluorescein

Fluorescein (0.25 g) dye is dissolved in an ethanol-water mixturecontaining 50 mL ethanol and 50 mL water. Dry weight of the Pure Visionsample is recorded. The samples are hydrated in pure water and the massis recorded. Following the hydration step, the samples are soaked in theethanol-water mixture containing fluorescein dye until a constant massis attained. The mass after soaking in the dye solution is recorded.Mass of the dye doped is calculated as the difference between the massafter soaking in the solution, and the dry mass multiplied by the massconcentration of the dye in the ethanol-water solution. Percentage ofthe dye doped is calculated as the ratio of mass of Fluorescein dyedoped over the dry mass multiplied by 100.

Example 4. Forming Structures in Balafilcon a Silicone Hydrogel

The optical system as described in Example 2 was used to form linesegments in select regions of hydrated balafilcon A (PureVision)silicone hydrogel materials. Experiments were conducted with and withoutthe photosensitizer, fluorescein.

As indicated in FIGS. 11A and 11B, the incorporation of fluorescein intoa balafilcon A silicone hydrogel provided a red shift in thetransmission spectrum of at least 150 nm. The balafilcon A siliconehydrogel with fluorescein has a relatively significant absorptionprofile at 500 nm (FIG. 12B), whereas a silicone hydrogel withoutphotosensitizer is essentially transparent at these wavelengths (FIG.12A).

FIG. 12A is phase contrast photograph of a balafilcon A siliconehydrogel that was micromachined at a depth of about 200 μm from the topirradiated surface. The irradiation process was conducted at 60 mW, anda constant scan rate of 0.5 μm/s. As indicated in FIG. 12A, therefractive line segments written in the balafilcon A silicone hydrogelwithout photosensitizer provide little, if any, change in refractiveindex, Δn<<0.005 (visible detection limit of the structures). In fact,it is very difficult to see the line segments in the material even withphase contrast enhancement. In contrast, as indicated in FIG. 12B, therefractive line segments written in the balafilcon A silicone hydrogelwith 0.17 wt. % fluorescein at the identical power and at a constantscan rate of 5.0 μm/s (a ten-fold increase over the undoped balafilconA) provide a very significant change in refractive index, ΔRI of about0.02 to 0.03. The refractive line segments are clearly visible withphase contrast enhancement. Moreover, even with a relatively low laserpower, i.e., 60 mW, one can still generate line segments with a Δn ofabout 0.01 with a constant scan rate of 1 mm/s.

FIG. 13 is a plot showing the change in refractive index vs. scan ratein balafilcon A materials; undoped or doped with fluorescein orcoumarin-1. The plot demonstrates the significant enhancement of thephoto-adjusting affect in the hydrogel material doped with aphotosensitizer. The doping of the material permits one to increase thescan rate of the laser through the material, i.e., form refractive linesegments in the material, by nearly 100-fold to achieve a comparablemodification of the refractive index in the material.

In Examples 2 and 4, the refractive structures (line segment arrays)were investigated by focusing an unpolarized He—Ne laser beam with awavelength of 632.8 nm on these arrays and monitoring the diffractionpattern. The diffraction angles showed good agreement with thediffraction equationmλ=d sin θ  (1)where m is the diffraction order, λ is the wavelength of the incidentlaser beam which here is 632.8 nm, and d is the grating period.

The diffraction efficiency of the written segment array can be measured,and since the efficiency is a function of the refractive index change,it may be used to calculate the refractive index change in the laserirradiation region. Consider the grating as a phase grating; itstransmittance function could be written as

$\begin{matrix}{{t\left( {x_{0},y_{0}} \right)} = {{\left( {e^{i\;\phi_{2}} - e^{i\;\phi_{1}}} \right){{rect}\left( \frac{x_{0}}{a} \right)}*\frac{1}{d}{{comb}\left( \frac{x_{0}}{d} \right)}} + e^{i\;\phi_{1}}}} & (2)\end{matrix}$where a is the grating line width, d is the groove spacing, ϕ₂ and ϕ₁are the phase delays through the lines and ambient region respectively,

${\phi_{2} = {{2\;\pi \times \frac{\left( {n + {\Delta\; n}} \right) \times b}{\lambda}\mspace{14mu}{and}\mspace{14mu}\phi_{1}} = {2\;\pi \times \frac{n \times b}{\lambda}}}},$b is the thickness of the grating line, n is the average refractiveindex of the material, Δn is the average refractive index change in thegrating lines, and λ is the incident light wavelength of the measurement(632.8 nm). Here, the grating line width is 1 μm and the thickness is 3μm. The index change within the laser effect region can be approximatedto be uniform. The convolution theorem can be used to calculate thespectrum of the grating such asT(f _(x) ,f _(y))=F{t(x ₀ ,y ₀)}=(e ^(iϕ) ² −e ^(iϕ) ¹ )a sin c(af_(x))comb(df _(x))δ(f _(y))+e ^(iϕ) ¹ δ(f _(x) ,f _(y))  (3)

Then, the intensity distribution of the grating diffraction pattern is:

$\begin{matrix}{{I\left( {x,y} \right)} = {\left( \frac{I}{\lambda\; z} \right)^{2} \times \left\lbrack {{\left( {e^{i\;\phi_{2}} - e^{i\;\phi_{1}}} \right)\frac{a}{d}{\sum\limits_{n = {- \infty}}^{\infty}\;{\sin\;{c\left( \frac{an}{d} \right)}{\delta\left( {{\frac{x}{\lambda\; z} - \frac{n}{d}},\frac{y}{\lambda\; z}} \right)}}}} + {e^{i\;\phi_{1}}{\delta\left( {\frac{x}{\lambda\; z},\frac{y}{\lambda\; z}} \right)}}} \right\rbrack^{2}}} & (4)\end{matrix}$

From this formula, the intensity of the 0th (I₀), 1st (I₁), and 2nd (I₂)order diffraction light is

$\begin{matrix}{I_{0} = {\left( \frac{1}{\lambda\; z} \right)^{2} \times \left\lbrack {{\left( {e^{i\; 2\;\pi \times \frac{{({n + {\Delta\; n}})} \times b}{\lambda}} - e^{i\; 2\;\pi \times \frac{n \times b}{\lambda}}} \right)\frac{a}{d}} + e^{i\; 2\;\pi \times \frac{n \times b}{\lambda}}} \right\rbrack^{2}}} & (5) \\{I_{1} = {\left( \frac{1}{\lambda\; z} \right)^{2} \times \left\lbrack {\left( {e^{i\; 2\;\pi \times \frac{{({n + {\Delta\; n}})} \times b}{\lambda}} - e^{i\; 2\;\pi \times \frac{n \times b}{\lambda}}} \right)\frac{a}{d}\sin\;{c\left( \frac{a}{d} \right)}} \right\rbrack^{2}}} & (6) \\{and} & \; \\{I_{2} = {\left( \frac{1}{\lambda\; z} \right)^{2} \times \left\lbrack {\left( {e^{i\; 2\;\pi \times \frac{{({n + {\Delta\; n}})} \times b}{\lambda}} - e^{i\; 2\;\pi \times \frac{n \times b}{\lambda}}} \right)\frac{a}{d}\sin\;{c\left( \frac{2a}{d} \right)}} \right\rbrack^{2}}} & (7)\end{matrix}$

By comparing the light intensities of 1^(st), 2^(nd) and 0^(th)diffraction orders, the refractive index change within the grating linescan be determined. FIG. 3 shows the ratio of intensity of the 1^(st) and2^(nd) diffraction order to 0^(th) order of the grating in PV2526-164 is0.1374 and 0.0842 respectively, and the corresponding refractive indexchange determined by the analysis is about 0.06. Using the same method,we determined the average refractive index change in RD1817 and HEMA Bto be 0.05±0.0005 and 0.03±0.0005. Thus, it was demonstrated that therefractive index of a material can be modified by applying an ultrafastlaser thereto.

Example 5

A femtosecond laser oscillator with a Kerr-lens mode-locked Ti:Sapphirelaser (MaiTai HP from Newport), generating pulses of 100 fs pulsewidthand 80 MHz repetition rate at a tunable wavelength range from 690 nm to1040 nm was used in the following Examples. In the experiments, theaverage laser power at the focus of the objective was attenuated andadjusted by a variable attenuator, and was set below 160 mW (2 nJ pulseenergy) to avoid gross optical damage in the hydrogel polymers. ThreeNewport VP-25XA linear servo stages with 100 nm resolution formed a 3Dsmooth scanning platform which was controlled and programmed by acomputer. The focusing objective was a 60× 0.70NA Olympus LUCPlanFLNlong-working-distance objective which could precisely correct thespherical aberration and create nearly diffraction-limited laser focalspot at different depths below the material surface.

During the laser pulse irradiation sequence, the optical, hydrogelpolymeric materials were maintained within an aqueous environment in asandwich structure between two coverslips, and mounted horizontally onthe scanning platform. The femtosecond laser pulses were focusedvertically inside the hydrogel samples through the focusing objective.Different horizontal, constant scanning speeds from 0.4 μm/s to 4 mm/swere used with different polymeric hydrogels and different average laserpower. A CCD camera was used to monitor the irradiation process anddetect plasma illumination, which indicated the onset of laser-inducedmaterial breakdown. After laser irradiation, the materials were removedand observed under a calibrated Olympus BX51 microscope with differentmodes. The change in refractive index of the irradiated regions weremeasured either by grating experiments as described in L. Ding et al.,“Large refractive index change in silicone-based and non-silicone-basedhydrogel polymers induced by femtosecond laser micro-machining,” Opt.Express 2006, 14, 11901-11909, or by a calibrated differentialinterference contrast (DIC) mode microscope.

Example 5A to 5D

Optical, hydrogel polymeric materials comprising hydroxyethylmethacrylate (HEMA), methylmethacrylate (MMA), ethylene glycoldimethacrylate (EGDMA) and variable concentrations offluorescein-methacrylate (Fluo-MA), were prepared and are summarized inTable 1. A master monomer batch containing HEMA (83.7 wt. %), MMA (13.7wt. %), EGDMA (0.51 wt. %) and AIBN (0.1 wt. %) initiator was prepared.An appropriate amount of Fluor-MA was added to separate monomerpreparations to provide monomer mixture with the stated wt. % ofFluor-MA listed in Table 1. The monomer mixtures were polymerizedaccording to well known methods in the art and cured in the form of 700μm-thick flat films.

The HEMA-based hydrogel polymers have a water content of about 28% byweight and an average refractive index of 1.44. An Ocean Optics HR4000spectrometer was usually used to measure their transmission spectra.

TABLE 1 Ex. No. 5A 5B 5C 5D 5E Fluor-MA — 0.0625 0.125 0.25 0.5

FIG. 14 shows the transmission spectra of the non-photosensitizedhydrogel material as well as the near identical hydrogel materials dopedwith different concentrations of Fluor-MA. As shown, the absorptionpeaks centered at about 350 nm to about 450 nm increased with anincrease in the Fluor-MA concentration. Each of the Fluor-MA dopedhydrogel materials remained transparent in the near infrared regionthough some scattering loss was observed at higher dopingconcentrations.

Each of the HEMA-based hydrogel materials were micromachined(irradiated) with femtosecond pulse sequence at 800 nm and 120 mWaverage power. Horizontal periodic line arrays were typically written˜100-150 μm beneath the top surface of the materials at differentconstant scanning speeds. The changes in refractive index with differentscanning speeds were measured for each material and are shown in FIG.15. The degree of change in refractive index decreased as the constantscanning speed increased. For example, the largest refractive indexchange in the non-doped material was about 0.03±0.005 at a scan speed of3 μm/s. Carbon damage spots were observed in the non-doped material ifthe scanning speed was less than 2 μm/s. Also, the degree of change inrefractive index decreased very quickly as the scanning speed increased.At a constant scanning speed greater than 10 μm/s, the changes inrefractive index were too small to be measured in our experiments(<0.005).

In contrast, with the doped hydrogel materials, we needed tosignificantly increase the scanning speed to avoid optical damage(carbonization) of the materials, which we believe is induced byaccumulated heat. For Example 5B with 0.0625% Fluo-MA, a constantscanning speed of at least 40 μm/s was required to avoid carbonizeddamage to the material. For Example 5E with 0.5% Fluo-MA one wouldobserve small spot evidence of damage within the material even at ascanning speed of 500 μm/s. Also, with irradiation of the Example 5E ata constant scanning speed of 600 μm/s, we measured a change in therefractive index of 0.085±0.005.

In general, the degree of change in the refractive index decreased asthe Fluor-MA doping concentration decreased with a constant scan speed.For example, with a scanning speed of 1 mm/s, the measured change inrefractive index for the 0.5% and 0.0625% Fluor-doped materials was0.065±0.005 and 0.005±0.002, respectively. In fact, for the 0.5% Fluo-MAmaterial, a change of refractive index of 0.025±0.005 was obtained at ascanning speed of 4 mm/s. These results indicate that nonlinearabsorption within the hydrogel polymers could be greatly increased ifFluo-MA is copolymerized into the polymer network.

Large changes in refractive index could be observed at constant scanningspeeds that are 1000× faster than for the non-doped material. If theFluor-MA concentration in the hydrogel materials of Example 5 was toohigh, i.e., greater than 3 wt %, we began to see aggregates (scatteringcenters) form within the hydrogel polymer network. Accordingly, for theHEMA-based materials of Example 5, the Fluor-MA concentration is fromabout 0.05 wt. % to about 2 wt. %, or from 0.1 wt. % to about 1.5 wt. %.To summarize, we have shown that as the concentration of thephotosensitizer monomer, Fluor-MA, in the polymeric hydrogels increased,we observed a corresponding increase in the degree of change inrefractive index within the focal volume even at significantly greaterconstant scan rates (FIG. 15).

FIGS. 16A and 16B summarize our experimental investigations with Example5A (non-doped) and Example 5E (0.5% Fluo-MA) using two different pulseenergies: (a) 1.5 nJ (120 mW average power); and (b) 2 nJ (160 mWaverage power). For both hydrogel materials, the degree of change inrefractive index decreased as the femtosecond laser was tuned to operateat a longer wavelength at a constant scan rate. For Example 5A, thedegree of change in refractive index was less than 0.01 for all laserwavelengths. An attempt to increase the pulse energy or decrease thescan rate resulted only in optical damage. For all wavelengths longerthan 850 nm, no change in refractive index was observed in Example 5A ateither pulse energy even if the scan rate was greater than 100 μm/s.Higher pulse energies and slower scan rates were also tested in thiswavelength region, but only optical damage with no change in refractiveindex was observed. In contrast, significantly large changes inrefractive index were measured in Example 5E. In addition, because ofthe nonlinear absorption enhancement provided by the photosensitizedmaterial, material damage was observed at the shorter wavelengths. Forexample, even with a scan rate of 2 mm/s and a pulse energy of 1.5 nJ,some optical damage is observed at wavelengths less than 775 nm.

The irradiation of Example 5E at longer wavelengths (greater than 800nm) did result in relatively large changes in refractive index withinthe focal volume of the material. FIG. 16A shows that one could achievea change in refractive index of 0.06 in the focal volume of the materialwith a constant scan rate of 0.5 mm/s at a wavelength of 900 nm. Also,by increasing the average laser pulse energy from 1.5 nJ to 2.0 nJ, onecould achieve even greater changes in refractive index, but some opticaldamage was observed. A comparison of the data and plots of FIG. 16A andFIG. 16B indicates that an increase in pulse energy from 1.5 nJ to 2 nJresults in optical damage at a wavelength of 900 nm and a scan rate of0.5 mm/s. Also, if the scan rate is increased to 1 mm/s, we observedvery small changes in refractive index (on the order of about 0.005).

To further investigate the wavelength dependence with respect to changesin refractive index within the focal volume, Examples 5A to 5E wereirradiated over a wavelength range from 700 nm to 1000 nm at differentscan rates and an average pulse energy of 1.5 nJ. For each hydrogelmaterial, the degree of change in refractive index decreased with anincrease in laser wavelength and increased with the Fluor-MAconcentration. FIG. 17 shows the data and plots of Example 5E at a scanrate of 1 mm/s. The data of FIG. 17 is very helpful because it suggestsa window of operating parameters in which one can form the refractivestructures in the hydrogel materials, and yet, remain a safe workingdistance from causing any significant optical damage (scatteringfeatures) in the materials. For Example 5D and 5E, irradiation at 850 nmto 900 nm provides a safe working distance from optical damage, and yetprovides a significant appreciable change in refractive index, i.e.,from 0.01 to 0.04, at the given scan rate and average laser power—onecan even see an appreciable change in refractive index at 950 nm forExample 5E.

As already stated, we believe that the presence of water within thepolymer matrix, as in the case of a hydrated hydrogel material, plays acritical part in forming the observed changes in refractive index withinthe focal volume. Accordingly, we investigated the effect of waterconcentration on the degree of change in refractive index in thehydrogel materials of Examples 5B to 5E as well as those of similarcomposition, but with reduced water content. A master monomer batchcontaining HEMA (68.6 wt. %), MMA (28.9 wt. %), EGDMA (0.51 wt. %) andAIBN (0.1 wt. %) initiator was prepared. An appropriate amount ofFluor-MA was added to separate monomer preparations to provide monomermixture with the stated wt. % of Fluor-MA listed in Table 2. The monomermixtures were polymerized according to well known methods in the art andcured in the form of 700 μm-thick flat films. The hydrogel polymers ofExample 6 have a 21% water content.

Likewise, the hydrogel materials of Example 7 were prepared from amaster monomer batch containing HEMA (49.0 wt. %), MMA (48.4 wt. %),EGDMA (0.51 wt. %) and AIBN (0.1 wt. %) initiator was prepared. Anappropriate amount of Fluor-MA was added to separate monomerpreparations to provide monomer mixture with the stated wt. % ofFluor-MA listed in Table 2. The monomer mixtures were polymerizedaccording to well known methods in the art and cured in the form of 700μm-thick flat films. The hydrogel polymers of Example 7 have a 12% watercontent.

TABLE 2 Ex. No. 6A 6B 6C 6D Fluor-MA 0.0625 0.125 0.25 0.5

TABLE 3 Ex. No. 7A 7B 7C 7D Fluor-MA 0.0625 0.125 0.25 0.5

As indicated, each set of materials of Examples 5 to 7 have varyingconcentrations of the photosensitizer, Fluo-MA. FIG. 18 shows theresulting change in refractive index in these hydrogel materials at anirradiation wavelength of 800 nm, 1.5 nJ average pulse energy and a scanrate of 1 mm/s. As shown, the degree of change in refractive indexdecreased as the water concentration decreased in all thephotosensitized hydrogel materials. We believe the localized waterconcentration of the hydrogel affects the thermodynamic properties suchas specific heat, heat capacity, etc. as well as the material density ofthe materials. The largest change in refractive index is obtained in thehydrogels of Example 5, which have the largest water content of about28%. Moreover, the hydrogels with relatively larger water contentprovide the largest safe working distance to form the refractivestructures without optical damage to the material.

We also investigated the wavelength dependence of the hydrogel materialsof Example 5E, Example 6D and Example 7D, each with 0.5% Fluor-MA, butwith the different water contents (see FIG. 19). A relatively largechange in refractive index (greater than 0.02) without any opticaldamage was observed only in Example 5E at an average pulse energy of 1.5nJ. One must note, however, that we also used a relatively fast scanrate of 1 mm/s in this investigation. As indicated, if the laserwavelength was less than about 750 nm, we observed only optical damage.If the laser pulses were operating at a wavelength greater than 800 nm,no change in refractive index is observed and optical damage is observedin the hydrogel materials of Example 7 (12% water content). For thehydrogel materials of Example 6 (21% water content), a change inrefractive index of 0.01 is observed without optical damage if theirradiation wavelength is about 875 nm. Optical hydrogel materials thatcan be used in the process described is prepared from polymeric monomerformulations listed in Table 4.

TABLE 4 range preferred range Formulation (wt. %) (wt. %) hydrophiliccomponent 65 to 90 78 to 90 alkyl(meth)acrylate component  5 to 20 10 to16 aromatic component  5 to 20 10 to 16 crosslinker 0.1 to 2.0 0.5photosensitizer 0.4 to 4.0 1.0 to 2.5 AIBN 0.05 to 0.5  0.05 to 0.3 

Optical hydrogel materials that can be used in the process described isprepared from polymeric monomer formulations listed in Table 5, and arelisted as Example 8 and 9. Examples 8 and 9 was thermally cured as 1 mmthick films by very gradual ramped heating to a maximum temperature of90° C. and subsequently sterilized by autoclaving. To obtain opticallyclear polymeric materials that were stable following the autoclaving ofthe materials it was necessary to include a solvent compatibilizerduring the polymerization. Such solvent compatibilizers include polororganic solvents such as ethyl acetate or DMF. The amount of solventcompatibilizer varied between 7 wt. % to 20 wt. % based on the totalweight of the monomeric components.

TABLE 5 Example 8 9 HEMA 84.5 83.6 MMA 13.8 13.7 EGDMA 0.5 0.5 Monomer X1 2 AIBN 0.1 0.1 Monomer X is2-[3′-tert-butyl-2′-hydroxy-5′-(3″-methacryloyloxypropoxy) phenyl]-5-chlorobenzotriazole: HEMA is 2-hydroxyethyl methacrylate: MMA is methylmethacrylate: EGDMA is ethylene glycol dimethacrylate; and AIBN isazobis(isobutyronitrile).Refractive Structures with a Gradient Index

Without exclusion as to any lens materials or material modifications,e.g., the inclusion of a photosensitizer, or laser parameters describedherein above, the foregoing disclosed techniques and apparatus can beused to modify the refractive properties, and thus, the dioptic power,of an optical polymeric material, typically, an optical hydrogelmaterial, in the form of, but not limited to, an IOL or corneal inlay,by creating (or machining) a refractive structure with a gradient indexin one, two or three dimensions of the optical material. The gradientrefractive structure can be formed by continuously scanning a continuousstream of femtosecond laser pulses having a controlled focal volume inand along at least one continuous segment (scan line) in the opticalmaterial while varying the scan speed and/or the average laser power,which creates a gradient refractive index in the polymer along thesegment. Accordingly, rather than creating discrete, individual, or evengrouped or clustered, adjoining segments of refractive structures with aconstant change in the index of refraction in the material, a gradientrefractive index is created within the refractive structure, and therebyin the optical material, by continuously scanning a continuous stream ofpulses. As will be described in greater detail below, since therefractive modification in the material arises from a multiphotonabsorption process, a well controlled focal volume corrected forspherical (and other) aberrations will produce a segment havingconsistent and, if desired, constant depth over the length of the scan.As further noted, when a tightly focused laser beam consisting offemtosecond pulses at high repetition rate impinges on a material thatis nominally transparent at the incident laser wavelength, there islittle if any effect on the material away from the focal region. In thefocal region, however, the intensity can exceed one terawatt per squarecentimeter, and the possibility of absorbing two or more photonssimultaneously can become significant. In particular, the amount oftwo-photon absorption can be adjusted by doping or otherwise includingin the irradiated material with selected chromophores that exhibit largetwo-photon absorption cross-section at the proper wavelength (e.g.,between 750 nm and 1100 nm), which can significantly increase thescanning speed as already described. Also, multiple segments can bewritten into the material in a layer using different scan speeds and/ordifferent average laser power levels for various segments to create agradient index profile across the layer, i.e., transverse to the scandirection. Further, multiple, spaced gradient index (GRIN) layers can bewritten into the material along the z-direction (i.e., generally thelight propagation direction through the material) to provide a desiredrefractive change in the material that corrects for some, most, or allhigher order aberrations of a patient's eye.

To write refractive GRIN layers or structures in the materials, it canbe advantageous to calibrate the effect of scanning speed and laserpower against a measured change in the refractive index of the materialwithin the focal volume. As an example, we prepared ten refractivestructures in the form of diffraction gratings at different writingspeeds while keeping all other parameters constant and measured theresulting diffraction efficiencies, and thereby determined the change inthe refractive index of the material.

FIG. 20 shows the refractive index change in an Akreos®-like material asa function of the scanning speed in mm/sec for a given set of operatingconditions: 400 mW average laser power, 100 fs pulse width, 800 nmwavelength, and focusing with a 0.7 NA air immersion microscopeobjective. FIG. 20 also shows an empirical fit to the data. Using thisempirical fit, one can obtain the scan speed as a function of desiredchange in refractive index change simply by inverting the relationship.Then, by using the calibration curve shown in FIG. 20, one can writerefractive structures that have a desired gradient index of refractionby changing the scanning speed. Alternatively, or in combination withchanging the scanning speed, one can write refractive structures thathave a desired gradient index by varying the laser (average) power.

For ophthalmic applications, it is of particular interest that the GRINrefractive structures are low scattering (as discussed above) and are ofhigh optical quality. FIG. 21 shows, in cross section, an ophthalmichydrogel material 600 having an anterior surface 602 and a posteriorsurface 604 in which lateral GRIN layers 605-N with a thickness of 1 μmto 10 μm, and separated by a distance between layers (in z-direction),have been written in an optical polymeric material. As indicated, light610 (shown in the form of waves) enters the optical material 600 throughthe anterior surface 602 and propagates through the material a distanceD before contacting the first of the gradient index layer 605-1. Eachgradient index layer 600-N comprises segments that can be written orformed as described above by scanning in the x direction or y direction.It is certainly to be understood by one of ordinary skill in the artthat one can also scan in any direction within a defined xy plane(rotation about the z-axis) or at any angle from 45° to 135° to thez-axis. To maintain simplicity in the description, however, the gradientlayers 600-N are shown at essentially 90° to the z-axis as well as theincoming light waves 610, and extend along, or are formed by scanningsegments (i.e., line segments) along, the x-axis. Again, to maintainsimplicity and for descriptive purposes only, the line segments alongthe scan direction are formed by maintaining a constant scan speed andconstant average laser power along the scan direction. Accordingly, eachline segment will provide a change in the index of refraction relativeto the index of the material that is constant along the scan direction.

Following the writing of one line segment along the x-direction, anadjacent line segment is written. The adjacent line segment could bewritten using the same scan speed and laser power thereby providing anidentical change in the index of refraction as the previously writtenline segment. Alternatively, the scan speed could be reduced with laserpower unchanged resulting in a greater change in the index of refractionas compared to the previous written line segment. As stated, to makecertain that there is little if no optical material between the adjacentsegments that escapes index modification the spacing between adjacentsegments is preferably less than the average line width of the twoadjacent segments. This process of writing line segments is continueduntil the desired number of segments is written with the desiredgradient index of refraction profile across the segments, i.e., across adimension of the GRIN layer.

Lastly, as the light waves pass through the plurality of GRIN layers605-N, the light waves bend with contribution from each GRIN layer andexit the posterior surface 604. The bending of the light waves providesa corrected wavefront 612, which provides a dioptic power change to thematerial, which in turn can be used to correct the vision of a patient.

FIG. 22 is representative of a GRIN layer written within the opticalmaterial by the process just described with respect to FIG. 21. FIG. 22is best described as a top view looking down upon the first gradientlayer 605-1 of FIG. 21. As shown, GRIN layer 605-1 comprises a pluralityN of line segments 705-1, 705-2, 705-3, . . . , 705-N that aresubstantially parallel and each line segment having a line width ofbetween about one to five μm (e.g., 2 μm, 3 μm, or 4 μm) and anintersegment spacing that is less than the segment line width (forsegments of approximately equal line width, as shown), or for variablesegment widths of two adjacent scan segments, the intersegment spacingis less than an average line width of the two adjacent scan segments. Inreference to FIG. 21, the segments are formed by scanning 4 mm along thex-direction, each segment written with a constant change in refractiveindex along the scan direction. It is noted that for descriptivepurposes only, the segments are numbered 705-1, 705-2, 705-3, . . . ,705-N, but each representative line segment is actually a collection ofseveral hundred line segments that have been written into the material.This is well understood by persons of skill in the art because oneimmediately recognizes that the depicted fifteen segments, each having aline width and intersegment spacing, for example, of 5 μm and 4 μm,respectively, would only cover a distance in y of about 60 μm, whereasthe actual structure formed extends about 1.8 mm in the y direction.Accordingly, the actual number of segments written is close to 4500total segments (each depicted segment representing about 300 writtensegments). Also, the white line segments depicted between each segmentare present only to distinguish the writing of each respective segment.In actuality, there is little or no spacing of non-index modifiedmaterial between segments. In particular, beginning from the far left ofgradient layer 605-1 each adjacent segment is written as one moveslaterally in the y-direction. In this one example, a total of fifteen(15) segments are represented or depicted until a desired width of thegradient layer is achieved. As shown, gradient layer 605-1 has a widthof 1.8 mm, and comprises a gradient index change along the y-directionand a constant index change along the x-direction.

As indicated, gradient index layer 605-1 includes a parabolic gradientindex profile with the change in the index of refraction increasing asone moves left in the y-direction from segment 705-1 to 705-8. Again,there are at least two ways one can provide an increase in the change ofindex across segments: one, to reduce the scan speed of respectivesegments as one moves along y, or to increase average laser power ofrespective segments as one moves along y. Of course, one of ordinaryskill can use other irradiation or optical conditions to achieve asimilar result. Once segment 705-8 is completed, the scan speed isincreased, or the average laser power decreased for segment 705-9,thereby setting a trend of a decrease in the change of index as onecontinues to move along in the y-direction until segment 705-15 iswritten.

FIGS. 23A and 23 B is a graphical representation of a gradient indexprofile of GRIN layer 605-1 of FIG. 22. FIG. 23A is a graphicalrepresentation of the change of index of refraction for selectedsegments 705-N of gradient layer 605-1. The stated change in the indexof refraction is in relation to the index of refraction of the opticalmaterial outside the focal volume. As indicated, segments 705-4 andcorresponding segment 705-12 are written with a selected scan speed andaverage laser power to provide a change in the index of refraction ofthe material of 0.02 along the entire segment length. Likewise, segments705-6 and corresponding segment 705-10 are written with a selected scanspeed and average laser power to provide a change in the index ofrefraction of the material of 0.03. Segment 705-8 is written with aselected scan speed and average laser power to provide a change in theindex of refraction of the material of 0.04. FIG. 23 B is a graphicalrepresentation of the gradient index profile along the y-axis ofgradient layer 605-1. Although FIG. 23B is depicted as a smoothcontinuous curve in the y-direction, one of ordinary skill in the artwould understand that there is likely to exist some variation orjaggedness in an actual gradient profile due in-part to the processdescribed and the dimensions involved with the focal volume and theability to accurately set scan coordinates of the laser system.

It is also understood by those of ordinary skill that the gradient indexprofile along the y-direction can have any preselected shape. Whereasthe gradient profile depicted in FIG. 23B will have an effect of apositive lens element one can just as easily prepare one or moregradient index layers with an inverted gradient profile, therebyproviding an effect of a negative lens element, FIG. 24.

In addition to, or as an alternative to, the gradient index profilebeing written along the y-direction, one can also write a gradient indexlayer along the scan direction. FIGS. 25A to 25C exemplify somepreferred gradient index profiles of a gradient layer along the scandirection. As stated, such a gradient layer can be formed by modulatinglaser power, or varying scan speed, during the scan, i.e., as eachsegment is being written. FIG. 25A exemplifies how the change inrefractive index of the material can increase at substantially aconstant rate along the entire scan direction. Likewise, one of ordinaryskill can also envision how the change in refractive index of thematerial can decrease at substantially a constant rate along the entirescan direction (not shown). FIG. 25B exemplifies how the change inrefractive index of the material can increase at substantially aconstant rate along half the scan direction to the midpoint of thesegment, and then decrease at a substantially a constant rate to the endof the segment. Likewise, one of ordinary skill can also envision howthe change in refractive index of the material can decrease atsubstantially a constant rate along half the scan direction to themidpoint of the segment, and then increase at a substantially a constantrate to the end of the segment (not shown). FIG. 25C exemplifies how thechange in refractive index of the material can increase at substantiallya constant rate to some transition point along the scan direction, andthen decrease at the same rate to the end of the segment. Likewise, oneof ordinary skill can also envision how the change in refractive indexof the material can decrease at substantially a constant rate to sometransition point along the scan direction, and then increase at the samerate to the end of the segment (not shown). The described gradient indexprofiles are provided for descriptive purpose only, and one of ordinaryskill in the art can certainly envision any number of gradient indexprofiles. For example, it is well understood by those in the art that achange in refractive index of the material along a segment can beconstant, or increase or decrease step wise or continuously along thesegment at more than one rate of change.

For every exemplary gradient index profile described above along thescan direction, a similar gradient index profile of the one or moregradient index layers can be achieved by varying the change of the indexof refraction across or between at least five or more adjacent segments(e.g., 5 to 1000 segments) of a GRIN layer, at least thirty or moreadjacent segments (e.g., 30 to 1000 segments), at least one hundred ormore adjacent segments (e.g., 100 to 1000 segments). FIGS. 26A to 26Cexemplify some preferred gradient index profiles of a gradient layeracross different segments, i.e., essentially transverse to the scandirection. As stated, such a gradient layer can be formed by modulatinglaser power, or varying scan speed in regions of adjacent segments. FIG.26A exemplifies how the change in refractive index of the material canincrease at substantially a constant rate along a series of adjacentsegments. Likewise, one of ordinary skill can also envision how thechange in refractive index of the material can decrease at substantiallya constant rate along a series of adjacent segments (not shown). FIG.26B exemplifies how the change in refractive index of the material canincrease at substantially a constant rate along a first region ofadjacent segments, and then proceed to decrease at a substantially aconstant rate along a second region of adjacent segments. Likewise, oneof ordinary skill can also envision how the change in refractive indexof the material can decrease at substantially a constant rate along afirst region of adjacent segments, and then proceed to increase at asubstantially a constant rate along a second region of adjacent segments(not shown). FIG. 25C exemplifies how the change in refractive index ofthe material can increase at substantially a constant rate along a firstregion of adjacent segments, and then proceed to decrease at a differentrate along a second region of adjacent segments.

FIGS. 26A to 26 C exemplify some gradient index profiles of the gradientindex layers transverse to the scan direction. By no means are thegradient profiles limited to these shapes. For example, it is wellunderstood by those in the art that a change in refractive index of thematerial across a plurality of segments can be constant, or increase ordecrease step wise or continuously along the segment at more than onerate of change.

When writing gradient index microstructures in ophthalmic devices, undersome conditions the accumulated phase difference in some regions of thestructure may exceed 2n. In those regions, the design of the gradientindex structure can be modified to provide a phase shift that ismodulo-2n. In other words, in the regions where the phase shift isbetween 2n and 4n, a constant phase shift of 2n can be subtracted fromthe total phase shift. Similarly, if the phase shift according to thedesign would place the phase shift in the range 4n to 6n, then aconstant 4n phase shift can be subtracted from the design in thatregion. This process for accounting for the phase shift can beadvantageous in some cases in helping to reduce the total device writingtimes.

As stated, change in the index of refraction will vary within eachgradient index layer in a prescribed manner according to the desiredfunctional requirements of the device. For instance, if a focusing lensis desired, it will be advantageous to have the change in the index ofrefraction vary quadratically. If the maximum index change is in thecenter and the change decreases outward to the edges, then the structurewill provide focusing power. In the reverse case, where the index changeis maximum at the edges and decreases toward the center, such astructure will provide divergence, or negative focusing power.Furthermore, if one or more layers 605 are written with a quadraticindex change of a given magnitude and orientation (e.g., x-direction)and one or more different layers are written with a quadratic indexchange of different magnitude and orientation (e.g., y-direction), anastigmatic crossed-cylindrical lens structure results, which isapplicable for vision correction in intraocular lenses. Refractivesegments can also be written as concentric segments radiating outwardlyfrom a central location, or as arcuate or curved segments. Also, therefractive segment can be written as a planar layer (of relativelyconstant thickness), or the refractive segment can vary in thez-direction, i.e., vary in thickness.

In an illustrative aspect, we wrote a cylindrical lens structure with aone-dimensional quadratic gradient index structure as shown in FIG. 21with three GRIN layers each 5 μm thick as illustrated in FIG. 22, spacedby 10 μm (z-direction). Accordingly, there exists a layer ofnon-modified optical material having a thickness of about 5 μm to 7 μmbetween each GRIN layer. The resulting cylindrical lens was designed toprovide approximately 1 diopter of astigmatism uniform along the lengthof the device.

FIG. 27 shows a Twyman Green interferometer image (FIG. 27B is aschematic representation of FIG. 27) of the lens structure 1801(rectangular region) showing nominally quadratic phase contours 1802 inthe lens area. The inset shows a phase topography measurement thatconfirms the parabolic nature of the phase readings. Imperfections inthe xyz high speed piezoelectric translation stage and scanningprocedure cause localized index fluctuations that result in random phaseshifts, but the general appearance of the fringes is as expected. Onecan speculate that the observed phase shifts is caused by anonuniformity in the scanning process, either in the scanning speed orin the line spacing. Furthermore, the 3D high speed ultrasonicpiezoelectric stages that we used (PolyTek PI) exhibited some retracingerrors wherein the return scan line was located a few microns below theheight of the initially scanned line, which could have caused somerandom phase errors. The measured astigmatism (corrected for anybaseline astigmatism in the glass and hydrogel substrate) varied between+0.3 and +0.9 diopters along the length of the sample.

Refractive structures having a gradient index are highly versatile, andcan be written, as described, as vertically spaced (z-direction) layerswith each GRIN layer being different in order to achieve differentresults. For hydrogel materials, e.g., in order to maintain high indexchange, it is advantageous to maintain a spacing between the GRIN layersin the range of 5 μm to 10 μm or so. For example, in order to keep thedevices compact, it is desirable to minimize the spacing between theGRIN layers, e.g., a spacing of 5 μm, 6 μm, 7 μm, 8 μm, or 9 μm.

It is desirable to be able to correct not only sphere and cylinder invision correction, but also higher-order aberrations. It is alsodesirable to provide advanced designs that can provide multi-focaleffects in order to alleviate symptoms of presbyopia. Furthermore, it isdesirable to minimize the effects of “rainbow,” which is adiffraction-based effect, in which diffracted peaks are seen at anglesmλ=d sin θ where m is the diffraction order, λ is the wavelength ofinterest, and d is the grating period. This effect is expected when theline spacing is larger than the wavelength of light being used forobservation. For example, in our development of the described GRINrefractive structures adjacent segments with intersegment spacing thatexceeded the average segment line width of the adjacent segmentsexhibited visible coloration or a rainbow effect, however by decreasingthe intersegment spacing to less than the average segment line width ofthe adjacent segments, e.g., 0.8 μm to 0.5 μm for an average segmentline width of 1 μm, the observed “rainbow” effect is significantlyreduced. With the intersegment spacing of the adjacent segments lessthan the average segment line width of the adjacent segments there is bynecessity some overlap in focal volumes of the adjacent segments.Accordingly, it is important to minimize any material damage that canresult from irradiating volumes of material more than once because weknow that material damage will cause light scattering.

In addition to the use of known adaptive optics systems and techniques,precise control of short light pulses from a laser to form refractivesegment(s) or gradient index layer(s) that can be written into an IOL ata depth of five mm (or more) from the front surface of a patient'scornea and into the IOL is described. High (nearly diffraction-limited)focus is maintained by an adaptive optic element with real-time feedbackduring scanning operations using an active feedback that is provided bya two-photon fluorescence signal.

It is known that high numerical aperture (NA>0.7) microscope objectiveseffectively used for writing refractive index modifications in a polymermaterial have a maximum working depth of about 3.2 mm. It is furtherappreciated that an implanted IOL may be located at a depth of 5 mm ormore behind the anterior corneal surface. Furthermore, aberrationsinduced at the corneal surface severely degrade the focused beamquality. The use of water immersion objectives provides increasedfocusing quality, but still with limited depth resolution. Also, the useof water immersion generally requires applanation of the corneal surfaceduring surgery. In addition, in order to write refractive correctionsinside the IOL, it will be preferred to scan regions of the cornea thatare significantly off-axis, which will introduce large higher orderaberrations and degrade the focused beam quality.

These recognized problems have encouraged a solution in the form of amethod and apparatus that can achieve diffraction-limited focusing withair immersion using a long working distance (e.g., up to 12 mm), high NA(i.e., >0.5) objective integrated with a scanning system that providesreal-time control of the focus and maintains it during the scanning orwriting process.

According to a non-limiting exemplary embodiment, an adaptive opticscanning system 1900 with real-time feedback is schematicallyillustrated in FIG. 28. A short pulse laser beam 1901 passes through acomputer controlled beam attenuator 1903 to set the desired laser power.The beam then passes through a magnifying relay telescope 1905 that isdesigned to optimally fill the input pupil of a microscope objective1976. The magnification and design of the relay lens system also is setto image a two dimensional galvanometer scanner 1907 into the inputpupil of the microscope objective. The two-dimensional galvanometerscanner can provide high speed re-targeting of the beam typically inabout 20 microseconds. After the galvanometer, the beam is reflectedfrom a deformable mirror 1904, which is controlled by a computer andchanges shape in response to signals from controller 1911. The light isfocused into the eye 1998 and into the interior of an implanted IOL 1999using a long working distance product inspection objective that has a100× NA 0.70 specification with a working distance of 10-12 mm (such asMitutoyo M PLAN NIR HR BF 100× NA 0.70, WD 10.0 mm or M PLAN NIR BF 100×NA 0.50, WD 12.0 mm). The Z-axis or focusing dimension is controlledwith a Z-axis scanner (not shown) that is attached to the microscopeobjective, whereas the X-Y scanning is provided by the galvanometersystem. Additional scanning components may be included that providescanning of the patient's head or, alternatively, scanning of theadaptive optic with the focusing lens.

In one optic system embodiment, an epi-mode (back-detected), exogenousor endogenous (from a two-photon chromophore that is used as atwo-photon enhancer in the IOL) two-photon fluorescence signal is usedas a detector of the focus quality. For example, a wavefront aberrationtest is initially conducted on a patient to determine the number andtype of refractive structures, preferably, the GRIN structuresdescribed, that are to be written into an IOL. Once the patient isappropriately positioned, a preliminary scan is done with the OCT(optical coherence tomography) system 1913 to locate the interfaces ofthe IOL. The laser is then operated at low power (˜5 mw) and thetwo-photon fluorescence signals are detected. The two-photonfluorescence signal at each of a defined grid of points is optimizedsuch that the two-photon signal is optimized at each scan point in theaberration correction grid. At each point, the optimum settings of thedeformable mirror can be determined that give the highest two-photonfluorescence signal. The settings are then saved for the scanning orwriting process. The laser is power is then increased and the scanningor writing of the refractive structures commences. At eachgalvo-scanning point, the deformable mirror returns to the wavefrontcorrection setting that provided the optimum focusing and the highesttwo-photon fluorescence signal, thereby providing nearlydiffraction-limited focusing throughout the scan region.

The aberration correction grid does not have to be as fine as themicromachining grid, but should be fine enough so that the aberrationsare corrected on a fine enough scale so that the focusing is maintainedat nearly diffraction-limit throughout the scanning process. Forexample, a rough correction grid could be used in combination with aninterpolation routine, and the aberration correction could beinterpolated inside the grid points for higher efficiency.

One must also consider to compensate for the optical aberrations thatresult when writing deep into a material. The use of a NA 0.7 microscopeobjective provides optimum experimental results in terms of dynamicrange (the range of index of refraction changes that can be obtainedabove baseline and before damage sets in). At such a high NA, it isnecessary to fully compensate the relevant aberrations, most importantlyspherical aberration.

Discussion of Gradient Index (GRIN) Layers

An xyz translation system can be used to write gradient index (GRIN)layers. The thin (1-10 μm) layers cause a variable phase shift in theplane, resulting in a curvature of the phase fronts of the light. FIG.29 shows a three-dimensional representation of a single, thin GRIN layerwritten into a flat piece of polymer material. As already discussedthere are several modes in which the refractive structures can bewritten. Since the gradient index of refraction change depends on thevariation in scan speed and/or the optical power, we can writerefractive devices using either mode, or both together. We refer tothese herein as “speed mode” and “power mode” for convenience.

1) In 1D Speed Mode, to write a single, thin GRIN layer, the translatoris first set to the required z-position to set the height of the layerinside the material. The translator is scanned along the y-direction ata speed that is uniform along y, and varies along x for one or morewritten segments. For instance, the speeds can be programmed to producea parabolic index change. This will produce a cylindrical lens withrefracting power in the x-direction that is uniform in the y-direction.In 2D Speed Mode, the translator is scanned along the y-direction at anon-uniform speed such that the index change is non-uniform along they-direction. The non-uniform y-speed can also be changed along thex-direction, resulting in a two-dimensional gradient index layer.

2) In 1D Power mode, to write a single, thin GRIN layer, the translatoris first set to the required z-position to set the height of the layerinside the material. The translator is scanned along the y-direction ata uniform speed and the intensity of the femtosecond laser pulses is setto a different average power by a light modulator such as anacousto-optic or electro-optic modulator for each y-scan. As a result,the index change is different for each x-position. For instance, theintensities may be set to produce a quadratic index variation along thex-direction. In 2D Power Mode, the light intensity is variedcontinuously along the y-scan during the y-scan, and the lightintensities can varied for each x-position. This results in atwo-dimensional gradient index layer.

Either of these techniques can be repeated, and after each layer iswritten along the z-axis, the GRIN layers are spaced or separated by 5to 10 microns, e.g., 6 microns, 7 microns, 8 microns or 9 microns. FIG.30 shows depicts three GRIN layers written into an optical polymericmaterial. Each individual GRIN layer can have the same or differentgradient index profile as the GRIN layer below or above. For instance,one layer may have the index gradient in the x-direction and anotherlayer may have the index gradient in the y-direction. This would resultin a “crossed cylinder” optical approach, which is similar to aspherical lens, except that it can offer certain design degrees offreedom.

3) Combined Speed and Power mode. In some cases, it may be advantageousto combine the speed and power modes. For instance, power mode could beused to vary the index change along the y-direction, and the scan speedscould be varied along the x-direction, and/or the reverse.

4) Galvanometer controlled systems. In the case of scanning systems thatrely upon galvanometer-type control systems, it is possible to addressdifferent points in the sample at high speeds in arbitrary patterns,resulting in complex gradient index possibilities. In this case, thelocalized index changes will depend on the laser power modulation andthe local scanning speed. Using a two dimensional galvo system with acustom designed optical relay lens system, we were able to write twodimensional, gradient index refractive structures in Thiol-ene typeoptical materials doped with ITX. FIG. 31 shows some preliminary resultsobtained by driving the galvanometers in out-of phase repetitivepatterns. These are commonly referred to as Lissajous patterns. It ispossible to write two-dimensional gradient index patterns with radiallysymmetric index gradient using such a system, and the control system forsuch a writing procedure could use a combination of variable scan speedcontrol and optical power control as discussed previously for the caseof xyz scanning.

Typically, galvo-controlled systems designed for high NA focusing arelimited to scanning over a small area (e.g., 350-450 μm diameter) as aresult of their short effective focal length. In order to writerelatively large refractive structures, a high NA large field opticalsystem is likely to be necessary. One can also stack the scanningsystems, for example, one can use a combination of galvo-scanning andsample translation. Planar gradient index structures such as those shownin FIG. 31 can be written in multiple layers also as shown in FIG. 31,and again, the gradient index profiles of each layer could be the sameor different.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted.

The recitation of ranges of values herein are merely intended to serveas a shorthand method of referring individually to each separate valuefalling within the range, unless otherwise indicated herein, and eachseparate value is incorporated into the specification as if it wereindividually recited herein.

All methods described herein can be performed in any suitable orderunless otherwise indicated herein or otherwise clearly contradicted bycontext. The use of any and all examples, or exemplary language (e.g.,“such as”) provided herein, is intended merely to better illuminateembodiments of the invention and does not impose a limitation on thescope of the invention unless otherwise claimed.

No language in the specification should be construed as indicating anynon-claimed element as essential to the practice of the invention.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the invention describedherein without departing from the spirit and scope of the invention.There is no intention to limit the invention to the specific form orforms disclosed, but on the contrary, the intention is to cover allmodifications, alternative constructions, and equivalents falling withinthe spirit and scope of the invention, as defined by the claims. Thus,it is intended that the invention cover the modifications and variationsof this invention provided they come within the scope of the appendedclaims and their equivalents.

We claim:
 1. A method for providing changes in refractive power of anoptical device, the method comprising: providing the optical device withan optical, polymeric lens material having an anterior surface andposterior surface and an optical axis intersecting the surfaces; andforming at least one laser-modified, gradient index (GRIN) layerdisposed between the anterior surface and the posterior surface withcontinuous streams of light pulses from a visible or near-IR laser byscanning the continuous streams of light pulses along regions of theoptical, polymeric material while varying the scan speed, the averagelaser power, or both, wherein the at least one laser-modified GRIN layercomprises a plurality of adjacent refractive segments having acontinuous change in the index of refraction in relation to the index ofrefraction of non-modified polymeric material, and the GRIN layer ischaracterized by a continuous variation in index of refraction of atleast one of: (i) a portion of the adjacent refractive segmentstransverse to the direction scanned; and (ii) a portion of therefractive segments along the direction scanned.
 2. The method of claim1, wherein the at least one laser-modified, GRIN layer disposed betweenthe anterior surface and the posterior surface is arranged along a firstaxis oriented between about 45° to 135° to the optical axis.
 3. Themethod of claim 1, wherein the polymeric lens material includes aphotosensitizer.
 4. The method of claim 3, wherein the photosensitizercomprises a chromophore having a two-photon, absorption cross-section ofat least 10 GM between a laser wavelength range of 750 nm to 1100 nm. 5.The method of claim 4, wherein the photosensitizer is part of apolymerizable monomer or is physically dispersed within the opticalpolymer.
 6. The method of claim 1, wherein scanning the light pulsesalong regions of the optical, polymeric material comprises a continuousstream of laser pulses having a pulse energy from 0.01 nJ to 20 nJ. 7.The method of claim 1, wherein the optical device is an intraocular lensor corneal inlay, and the forming of the at least one laser-modifiedGRIN layer is performed following the surgical placement of the opticaldevice in an eye of a patient.
 8. The method of claim 1, wherein theplurality of adjacent refractive segments have an independent line widthof one to five μm and an intersegment spacing of two adjacent refractivesegments is less than an average line width of the two adjacentsegments.
 9. The method of claim 1, wherein the plurality of adjacentrefractive segments are essentially parallel segments.
 10. The method ofclaim 2, wherein the plurality of adjacent refractive segments areconcentric segments outwardly projected from a central point along thefirst axis.
 11. The method of claim 1, wherein the plurality of adjacentrefractive segments are arcuate or curved segments.
 12. The method ofclaim 1, wherein the plurality of adjacent refractive segments of theGRIN layer are characterized by a constant positive change in the indexof refraction of at least one of: (i) a portion of the refractivesegments transverse to the direction scanned; and (ii) a portion of therefractive segments along the direction scanned.
 13. The method of claim1, wherein the plurality of adjacent refractive segments of the GRINlayer are characterized by a constant rate of increasing or decreasingpositive change in the index of refraction of at least one of: (i) aportion of the refractive segments transverse to the direction scanned;and (ii) a portion of the refractive segments along the directionscanned.
 14. The method of claim 1, wherein the at least onelaser-modified, GRIN layer has a quadratic profile.
 15. The method ofclaim 1, wherein the at least one laser-modified, GRIN layer exhibitslittle or no scattering loss.
 16. The method of claim 1 wherein theforming the at least one laser-modified, GRIN layer includes formingfrom two to ten laser-modified, GRIN layers.
 17. The method of claim 2wherein the forming the at least one laser-modified, GRIN layer includesforming from two to ten laser-modified, GRIN layers arranged eitherabove or below the at least one laser-modified, GRIN layer.
 18. Themethod of claim 17 wherein each GRIN layer has an independent thicknessof from two μm to ten μm, and the plurality of GRIN layers exhibitlittle or no scattering loss.
 19. The method of claim 17 wherein the twoto ten GRIN layers has an interlayer spacing of non-modified polymericlens material having a thickness of from five μm to 10 μm.
 20. Themethod of claim 1, wherein the plurality of adjacent refractive segmentsof the at least one laser-modified, GRIN layer are characterized by aconstant rate of increasing or decreasing change in the index ofrefraction of a portion of the plurality of refractive segments alongthe direction scanned.
 21. The method of claim 1, wherein the pluralityof adjacent refractive segments each have an independent line width andan intersegment spacing of two adjacent refractive segments is less thanan average line width of the two adjacent segments so that there isoverlap of the adjacent segments.
 22. The method of claim 1, wherein theoptical device is a contact lens.
 23. The method of claim 22, whereinthe at least one laser-modified, GRIN layer formed in the contact lenscorrects for astigmatism.
 24. The method of claim 22, wherein the atleast one laser-modified, GRIN layer formed in the contact lens correctsfor higher-order aberrations.
 25. The method of claim 22, wherein the atleast one laser-modified, GRIN layer formed in the contact lens createsa multifocal lens.